GSH

evidence_span

{"source_cache": "artifacts/copper-research/18458339.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e2740a864c2c21568eae7933027e4c9bb16b985478ebbf946d4d2067ba777f8", "start_char": 0, "end_char": 1482, "text_sha256": "1e2740a864c2c21568eae7933027e4c9bb16b985478ebbf946d4d2067ba777f8"}

experimental_model

Purified-protein metal and electron transfer experiments

exposure

Defined COX17 and SCO redox states; glutathione reduction

limitations

Biochemical transfer mechanism; the same coupled reaction was not observed with SCO2. These results are not proof that glutathione supplementation repairs COX assembly.

nutrient_topic

Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper

organism

Human proteins

plain_language

Glutathione helps reset a mitochondrial copper courier.

primary_references

[copper-p18458339] Mitochondrial copper(I) transfer from Cox17 to Sco1 is coupled to electron transfer. (2008). https://pubmed.ncbi.nlm.nih.gov/18458339/ DOI: 10.1073/pnas.0800019105

tissue_or_cell_type

Mitochondrial intermembrane-space protein system

Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 624–635

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified-protein metal and electron transfer experiments · source_derived_draft · unverified_draft

### copper-glutathione-cox17-recycling Glutathione reduced fully oxidized apo-COX17 back to the two-disulfide state in the protein-transfer system. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione helps reset a mitochondrial copper courier. organism: Human proteins tissue_or_cell_type: Mitochondrial intermembrane-space protein system experimental_model: Purified-protein metal and electron transfer experiments limitations: Biochemical transfer mechanism; the same coupled reaction was not observed with SCO2. These results are not proof that glutathione supplementation repairs COX assembly. exposure: Defined COX17 and SCO redox states; glutathione reduction evidence_span: {"source_cache": "artifacts/copper-research/18458339.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e2740a864c2c21568eae7933027e4c9bb16b985478ebbf946d4d2067ba777f8", "start_char": 0, "end_char": 1482, "text_sha256": "1e2740a864c2c21568eae7933027e4c9bb16b985478ebbf946d4d2067ba777f8"} [copper-p18458339] Mitochondrial copper(I) transfer from Cox17 to Sco1 is coupled to electron transfer. (2008). https://pubmed.ncbi.nlm.nih.gov/18458339/ DOI: 10.1073/pnas.0800019105

evidence_access

Primary abstract

experimental_model

Human A549 cytokine-stimulation experiment.

limitations

The experiment supports a chemical-reactivity dependency; it does not establish a human supplement interaction magnitude.

nutrient_topic

Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins

plain_language

A separately stored thiol changed the signaling result.

primary_references

Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 220–226

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human A549 cytokine-stimulation experiment. · source_derived_draft · unverified_draft

## cucurbitacin-b-gsh-icam-rescue A separately stored thiol changed the signaling result. Adding glutathione attenuated cucurbitacin B inhibition of TNF-alpha-induced ICAM1 expression; L-cysteine had a smaller effect than the other tested thiols. Model: Human A549 cytokine-stimulation experiment. Limitations: The experiment supports a chemical-reactivity dependency; it does not establish a human supplement interaction magnitude. Evidence access: Primary abstract Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130

evidence_access

Primary abstract

experimental_model

Two cell lines with different susceptibilities; identities not provided in accessed abstract.

limitations

The proposed intracellular peroxovanadium sequence was not established as a universal mechanism.

nutrient_topic

Vanadium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Vanadium

plain_language

Available reducing or peroxide-removing capacity changed the toxicity response.

primary_references

Mechanisms of vanadate-induced cellular toxicity: role of cellular glutathione and NADPH. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12234491/ · DOI 10.1016/s0003-9861(02)00408-3

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 142–148

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Two cell lines with different susceptibilities; identities not provided in accessed abstract. · source_derived_draft · unverified_draft

## vanadium-gsh-cell-rescue Available reducing or peroxide-removing capacity changed the toxicity response. Glutathione and catalase reversed vanadate sensitivity in the susceptible cell line studied. Model: Two cell lines with different susceptibilities; identities not provided in accessed abstract. Limitations: The proposed intracellular peroxovanadium sequence was not established as a universal mechanism. Evidence access: Primary abstract Mechanisms of vanadate-induced cellular toxicity: role of cellular glutathione and NADPH. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12234491/ · DOI 10.1016/s0003-9861(02)00408-3

evidence_span

{"source_cache": "artifacts/ceylon-research/26851241.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2", "start_char": 0, "end_char": 1591, "text_sha256": "c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2"}

experimental_model

Recombinant human CYP assays and mechanistic static modeling

exposure

Cinnamaldehyde, NADPH and glutathione; modeled inhibitor concentrations 0.1 and 1 micromolar

limitations

Enzyme inhibition and model predictions are not measured clinical drug interactions. NADPH omission is not dietary niacin deficiency.

nutrient_topic

Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. · Ceylon cinnamon / Cinnamomum verum bark preparations

organism

Human enzyme preparations; computational model

plain_language

Glutathione partially buffered this enzyme effect in the assay; supplement protection was not tested.

primary_references

[ceylon-p26851241] Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole. (2016). https://pubmed.ncbi.nlm.nih.gov/26851241/ DOI: 10.1124/dmd.115.067942

tissue_or_cell_type

CYP2A6 reaction system

Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17) · lines 740–751

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human CYP assays and mechanistic static modeling · source_derived_draft · unverified_draft

### ceylon-gsh-cyp Added glutathione modestly but significantly reduced the extent of cinnamaldehyde-dependent CYP2A6 inhibition. Condition category: normal nutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione partially buffered this enzyme effect in the assay; supplement protection was not tested. organism: Human enzyme preparations; computational model tissue_or_cell_type: CYP2A6 reaction system experimental_model: Recombinant human CYP assays and mechanistic static modeling limitations: Enzyme inhibition and model predictions are not measured clinical drug interactions. NADPH omission is not dietary niacin deficiency. exposure: Cinnamaldehyde, NADPH and glutathione; modeled inhibitor concentrations 0.1 and 1 micromolar evidence_span: {"source_cache": "artifacts/ceylon-research/26851241.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2", "start_char": 0, "end_char": 1591, "text_sha256": "c2fb6b18a3ba708f060d53011ea0e198f98fe980930297e714c488a41413b5a2"} [ceylon-p26851241] Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole. (2016). https://pubmed.ncbi.nlm.nih.gov/26851241/ DOI: 10.1124/dmd.115.067942

evidence_span

{"source_cache": "artifacts/sulforaphane-research/7826396.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe", "start_char": 0, "end_char": 989, "text_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe"}

experimental_model

Recombinant human GST conjugation and reverse-reaction kinetics

exposure

Four isothiocyanates and GSTP1-1, GSTM1-1, GSTA1-1 and GSTM2-2

limitations

Relative enzyme rates are not whole-person clearance predictions; reverse reactions were slower and inhibited by high GSH.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human GST isoenzymes

plain_language

Glutathione is a reacting molecule here, not merely an antioxidant label.

primary_references

[sulforaphane-p7826396] Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases. (1995). https://pubmed.ncbi.nlm.nih.gov/7826396/ DOI: 10.1006/bbrc.1995.1106

tissue_or_cell_type

Isothiocyanate-glutathione chemistry

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 281–292

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human GST conjugation and reverse-reaction kinetics · source_derived_draft · unverified_draft

### sulforaphane-gsh-conjugation Sulforaphane underwent both nonenzymatic and GST-catalyzed conjugation with glutathione. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione is a reacting molecule here, not merely an antioxidant label. organism: Human GST isoenzymes tissue_or_cell_type: Isothiocyanate-glutathione chemistry experimental_model: Recombinant human GST conjugation and reverse-reaction kinetics limitations: Relative enzyme rates are not whole-person clearance predictions; reverse reactions were slower and inhibited by high GSH. exposure: Four isothiocyanates and GSTP1-1, GSTM1-1, GSTA1-1 and GSTM2-2 evidence_span: {"source_cache": "artifacts/sulforaphane-research/7826396.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe", "start_char": 0, "end_char": 989, "text_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe"} [sulforaphane-p7826396] Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases. (1995). https://pubmed.ncbi.nlm.nih.gov/7826396/ DOI: 10.1006/bbrc.1995.1106

evidence_span

{"source_cache": "artifacts/sulforaphane-research/9637733.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4e7a66b2c4a636f70f2a5954ff304e54d4ef0f00055e53bc32ba8ceb9772fbe2", "start_char": 0, "end_char": 1258, "text_sha256": "4e7a66b2c4a636f70f2a5954ff304e54d4ef0f00055e53bc32ba8ceb9772fbe2"}

experimental_model

Purified recombinant subunit/holoenzyme kinetics

exposure

Substrate comparisons and glutathione inhibition

limitations

Baseline enzymology, not a sulforaphane or nutrient-repletion trial.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human GCLC and GCLM expressed in insect cells

plain_language

The product feeds back on the machinery that makes more of it.

primary_references

[sulforaphane-p9637733] Expression and characterization of human glutamate-cysteine ligase. (1998). https://pubmed.ncbi.nlm.nih.gov/9637733/ DOI: 10.1006/abbi.1998.0676

tissue_or_cell_type

Glutathione synthesis first-step enzyme

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 827–838

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant subunit/holoenzyme kinetics · source_derived_draft · unverified_draft

### sulforaphane-gsh-feedback Glutathione inhibited both human GCLC and GCL holoenzyme, with greater sensitivity of GCLC alone. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The product feeds back on the machinery that makes more of it. organism: Human GCLC and GCLM expressed in insect cells tissue_or_cell_type: Glutathione synthesis first-step enzyme experimental_model: Purified recombinant subunit/holoenzyme kinetics limitations: Baseline enzymology, not a sulforaphane or nutrient-repletion trial. exposure: Substrate comparisons and glutathione inhibition evidence_span: {"source_cache": "artifacts/sulforaphane-research/9637733.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4e7a66b2c4a636f70f2a5954ff304e54d4ef0f00055e53bc32ba8ceb9772fbe2", "start_char": 0, "end_char": 1258, "text_sha256": "4e7a66b2c4a636f70f2a5954ff304e54d4ef0f00055e53bc32ba8ceb9772fbe2"} [sulforaphane-p9637733] Expression and characterization of human glutamate-cysteine ligase. (1998). https://pubmed.ncbi.nlm.nih.gov/9637733/ DOI: 10.1006/abbi.1998.0676

evidence_span

{"source_cache": "artifacts/chromium-research/18808157.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ed2c80b5da41d110da38bc0ed29d900d1d33f4180b64e13cb9b24ae7da5e1cdb", "start_char": 0, "end_char": 1724, "text_sha256": "ed2c80b5da41d110da38bc0ed29d900d1d33f4180b64e13cb9b24ae7da5e1cdb"}

experimental_model

Cell-free chromate reduction followed by plasmid replication in human fibroblasts

exposure

2 versus 5 mM glutathione with Cr(VI)

limitations

Toxicology assay, not oral chromium exposure. Proposed crosslink identities depend on preparation and analytical methods; later work questions some pre-reacted ternary-adduct preparations.

nutrient_topic

Chromium research collection; topical membership is not evidence of a direct dietary effect. · Chromium

organism

Chemical system with human fibroblast mutagenicity readout

plain_language

The authors detected and assigned a glutathione-linked DNA lesion; the preparation and analytical assignment matter.

primary_references

[chromium-p18808157] Reduction with glutathione is a weakly mutagenic pathway in chromium(VI) metabolism. (2008). https://pubmed.ncbi.nlm.nih.gov/18808157/ DOI: 10.1021/tx800265g

tissue_or_cell_type

DNA reaction mixture and reporter plasmid

Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 1173–1184

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free chromate reduction followed by plasmid replication in human fibroblasts · source_derived_draft · unverified_draft

### chromium-gsh-chromate-adducts The study attributed about 5% of total chromium-DNA adducts to GSH-Cr-DNA crosslinks at 2 mM glutathione, with four- to fivefold higher crosslinking at 5 mM. Condition category: normal nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The authors detected and assigned a glutathione-linked DNA lesion; the preparation and analytical assignment matter. organism: Chemical system with human fibroblast mutagenicity readout tissue_or_cell_type: DNA reaction mixture and reporter plasmid experimental_model: Cell-free chromate reduction followed by plasmid replication in human fibroblasts limitations: Toxicology assay, not oral chromium exposure. Proposed crosslink identities depend on preparation and analytical methods; later work questions some pre-reacted ternary-adduct preparations. exposure: 2 versus 5 mM glutathione with Cr(VI) evidence_span: {"source_cache": "artifacts/chromium-research/18808157.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ed2c80b5da41d110da38bc0ed29d900d1d33f4180b64e13cb9b24ae7da5e1cdb", "start_char": 0, "end_char": 1724, "text_sha256": "ed2c80b5da41d110da38bc0ed29d900d1d33f4180b64e13cb9b24ae7da5e1cdb"} [chromium-p18808157] Reduction with glutathione is a weakly mutagenic pathway in chromium(VI) metabolism. (2008). https://pubmed.ncbi.nlm.nih.gov/18808157/ DOI: 10.1021/tx800265g

evidence_span

{"source_cache": "artifacts/chromium-research/18808157.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ed2c80b5da41d110da38bc0ed29d900d1d33f4180b64e13cb9b24ae7da5e1cdb", "start_char": 0, "end_char": 1724, "text_sha256": "ed2c80b5da41d110da38bc0ed29d900d1d33f4180b64e13cb9b24ae7da5e1cdb"}

experimental_model

Cell-free chromate reduction followed by plasmid replication in human fibroblasts

exposure

2 versus 5 mM glutathione with Cr(VI)

limitations

Toxicology assay, not oral chromium exposure. Proposed crosslink identities depend on preparation and analytical methods; later work questions some pre-reacted ternary-adduct preparations.

nutrient_topic

Chromium research collection; topical membership is not evidence of a direct dietary effect. · Chromium

organism

Chemical system with human fibroblast mutagenicity readout

plain_language

More glutathione did not simply mean less damage in this chemical system.

primary_references

[chromium-p18808157] Reduction with glutathione is a weakly mutagenic pathway in chromium(VI) metabolism. (2008). https://pubmed.ncbi.nlm.nih.gov/18808157/ DOI: 10.1021/tx800265g

tissue_or_cell_type

DNA reaction mixture and reporter plasmid

Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 1160–1171

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free chromate reduction followed by plasmid replication in human fibroblasts · source_derived_draft · unverified_draft

### chromium-gsh-chromate-mutagenesis Chromate reduction with 2 mM glutathione produced weak plasmid mutagenicity; 5 mM glutathione produced about four times the mutation yield per DNA adduct. Condition category: normal nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: More glutathione did not simply mean less damage in this chemical system. organism: Chemical system with human fibroblast mutagenicity readout tissue_or_cell_type: DNA reaction mixture and reporter plasmid experimental_model: Cell-free chromate reduction followed by plasmid replication in human fibroblasts limitations: Toxicology assay, not oral chromium exposure. Proposed crosslink identities depend on preparation and analytical methods; later work questions some pre-reacted ternary-adduct preparations. exposure: 2 versus 5 mM glutathione with Cr(VI) evidence_span: {"source_cache": "artifacts/chromium-research/18808157.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ed2c80b5da41d110da38bc0ed29d900d1d33f4180b64e13cb9b24ae7da5e1cdb", "start_char": 0, "end_char": 1724, "text_sha256": "ed2c80b5da41d110da38bc0ed29d900d1d33f4180b64e13cb9b24ae7da5e1cdb"} [chromium-p18808157] Reduction with glutathione is a weakly mutagenic pathway in chromium(VI) metabolism. (2008). https://pubmed.ncbi.nlm.nih.gov/18808157/ DOI: 10.1021/tx800265g

evidence_span

{"source_cache": "artifacts/chromium-research/8605085.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19976d36625bfcd29ba9739717e4b5ee7c2a641dc625a2bfed62947df7060889", "start_char": 0, "end_char": 1103, "text_sha256": "19976d36625bfcd29ba9739717e4b5ee7c2a641dc625a2bfed62947df7060889"}

experimental_model

Oral radiotracer retention and distribution experiments

exposure

Labeled oral chromium with dietary/metabolite coadministration

limitations

A negative retention result in this preparation does not exclude all chemical complexation or dose effects. Oral coadministration is not identical to a preformed chromium-nicotinate complex.

nutrient_topic

Chromium research collection; topical membership is not evidence of a direct dietary effect. · Chromium

organism

Rat

plain_language

Adding glutathione did not make the rats retain more chromium in this experiment.

primary_references

[chromium-p8605085] Dietary and metabolite effects on trivalent chromium retention and distribution in rats. (1995). https://pubmed.ncbi.nlm.nih.gov/8605085/ DOI: 10.1007/bf02789412

tissue_or_cell_type

Whole-body and tissue chromium

Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 874–885

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oral radiotracer retention and distribution experiments · source_derived_draft · unverified_draft

### chromium-gsh-retention-null Oral coadministration of glutathione with labeled chromium did not significantly alter chromium retention in the rat study. Condition category: normal nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding glutathione did not make the rats retain more chromium in this experiment. organism: Rat tissue_or_cell_type: Whole-body and tissue chromium experimental_model: Oral radiotracer retention and distribution experiments limitations: A negative retention result in this preparation does not exclude all chemical complexation or dose effects. Oral coadministration is not identical to a preformed chromium-nicotinate complex. exposure: Labeled oral chromium with dietary/metabolite coadministration evidence_span: {"source_cache": "artifacts/chromium-research/8605085.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19976d36625bfcd29ba9739717e4b5ee7c2a641dc625a2bfed62947df7060889", "start_char": 0, "end_char": 1103, "text_sha256": "19976d36625bfcd29ba9739717e4b5ee7c2a641dc625a2bfed62947df7060889"} [chromium-p8605085] Dietary and metabolite effects on trivalent chromium retention and distribution in rats. (1995). https://pubmed.ncbi.nlm.nih.gov/8605085/ DOI: 10.1007/bf02789412

evidence_span

{"source_cache": "artifacts/curcumin-research/29097552.publisher-preview.txt", "locator": "Primary public publisher preview, reference superscripts removed; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fe26fe4a94e0ab5b60d128b86deb5bc8723e13a0403fcbdba7ef97224a22ef9a", "start_char": 0, "end_char": 2711, "text_sha256": "fe26fe4a94e0ab5b60d128b86deb5bc8723e13a0403fcbdba7ef97224a22ef9a"}

experimental_model

Curcumin analog chemistry and stimulated cellular NF-kappa-B assays

exposure

Curcumin, oxidation-resistant analogs and inhibition of glutathione biosynthesis

limitations

Mechanistic bioactivation evidence in experimental systems, not proof that every oral formulation inhibits human NF-kappa-B.

nutrient_topic

Curcumin research collection; topical membership is not evidence of a direct dietary effect. · Curcumin

organism

Cellular and purified-kinase systems; species not assigned from abstract

plain_language

Glutathione can intercept reactive curcumin-derived material.

primary_references

[curcumin-p29097552] The anti-inflammatory activity of curcumin is mediated by its oxidative metabolites. (2017). https://pubmed.ncbi.nlm.nih.gov/29097552/ DOI: 10.1074/jbc.ra117.000123

tissue_or_cell_type

Oxidative metabolite, protein-adduct and glutathione measurements

Curcumin: metabolism, signaling and nutrient connections (2026-09-17) · lines 463–474

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Curcumin analog chemistry and stimulated cellular NF-kappa-B assays · source_derived_draft · unverified_draft

### curcumin-gsh-adduct Curcumin-derived glutathione adducts were measured in cells. Condition category: normal nutrient_topic: Curcumin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione can intercept reactive curcumin-derived material. organism: Cellular and purified-kinase systems; species not assigned from abstract tissue_or_cell_type: Oxidative metabolite, protein-adduct and glutathione measurements experimental_model: Curcumin analog chemistry and stimulated cellular NF-kappa-B assays limitations: Mechanistic bioactivation evidence in experimental systems, not proof that every oral formulation inhibits human NF-kappa-B. exposure: Curcumin, oxidation-resistant analogs and inhibition of glutathione biosynthesis evidence_span: {"source_cache": "artifacts/curcumin-research/29097552.publisher-preview.txt", "locator": "Primary public publisher preview, reference superscripts removed; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fe26fe4a94e0ab5b60d128b86deb5bc8723e13a0403fcbdba7ef97224a22ef9a", "start_char": 0, "end_char": 2711, "text_sha256": "fe26fe4a94e0ab5b60d128b86deb5bc8723e13a0403fcbdba7ef97224a22ef9a"} [curcumin-p29097552] The anti-inflammatory activity of curcumin is mediated by its oxidative metabolites. (2017). https://pubmed.ncbi.nlm.nih.gov/29097552/ DOI: 10.1074/jbc.ra117.000123

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Explains why B2-dependent GSH recycling and selenium-dependent GSH use are distinct requirements.

evidence_location

Abstract

experimental_model

Erythrocyte hemolyzates from selenium-deficient rats; glutathione addition during peroxide/ascorbate challenge and 75Se enzyme purification.

exposure

Selenium-deficient diet, then ex-vivo oxidant and glutathione exposure

limitations

Separate from FAD-dependent GSR recycling; neither riboflavin nor combined nutrient repletion was tested.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Rattus norvegicus

plain_language

Supplying glutathione did not replace the missing selenium-dependent enzyme activity.

primary_references

[rotruck1973] Selenium: biochemical role as a component of glutathione peroxidase. (1973). https://pubmed.ncbi.nlm.nih.gov/4686466/ DOI: 10.1126/science.179.4073.588

tissue_or_cell_type

Erythrocyte hemolyzates

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1472–1484

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Erythrocyte hemolyzates from selenium-deficient rats; glutathione addition during peroxide/ascorbate challenge and 75Se enzyme purification. · source_derived_draft · unverified_draft

### b2-redox-gsh-needs-selenium-peroxidase Added glutathione failed to protect hemoglobin during oxidant challenge of selenium-deficient rat hemolyzates with very low glutathione-peroxidase activity. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Supplying glutathione did not replace the missing selenium-dependent enzyme activity. organism: Rattus norvegicus tissue_or_cell_type: Erythrocyte hemolyzates experimental_model: Erythrocyte hemolyzates from selenium-deficient rats; glutathione addition during peroxide/ascorbate challenge and 75Se enzyme purification. limitations: Separate from FAD-dependent GSR recycling; neither riboflavin nor combined nutrient repletion was tested. exposure: Selenium-deficient diet, then ex-vivo oxidant and glutathione exposure cross_nutrient: Explains why B2-dependent GSH recycling and selenium-dependent GSH use are distinct requirements. evidence_location: Abstract [rotruck1973] Selenium: biochemical role as a component of glutathione peroxidase. (1973). https://pubmed.ncbi.nlm.nih.gov/4686466/ DOI: 10.1126/science.179.4073.588

evidence_access

Primary abstract

experimental_model

Cell-free singlet-oxygen chemistry.

limitations

Regeneration was proposed; its complete cellular enzymatic cycle was not established.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

Glutathione changes the fate of oxidized ergothioneine.

primary_references

Ergothioneine stands out from hercynine in the reaction with singlet oxygen: Resistance to glutathione and TRIS in the generation of specific products indicates high reactivity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29074402/ · DOI 10.1016/j.freeradbiomed.2017.10.372

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 144–150

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free singlet-oxygen chemistry. · source_derived_draft · unverified_draft

## ergothioneine-glutathione-preservation Glutathione changes the fate of oxidized ergothioneine. In the singlet-oxygen assay, 5 mM glutathione almost abolished net ergothioneine loss even though formation of selected products persisted. Model: Cell-free singlet-oxygen chemistry. Limitations: Regeneration was proposed; its complete cellular enzymatic cycle was not established. Evidence access: Primary abstract Ergothioneine stands out from hercynine in the reaction with singlet oxygen: Resistance to glutathione and TRIS in the generation of specific products indicates high reactivity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29074402/ · DOI 10.1016/j.freeradbiomed.2017.10.372

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Macrophage culture with serine restriction and metabolite add-back.

limitations

The delivered compound was cell-permeable GSH, not an assumed effect of oral glutathione.

nutrient_topic

L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine

plain_language

The limiting branch differs from the nucleotide requirement in dividing T cells.

primary_references

Serine Metabolism Supports Macrophage IL-1β Production. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30773464/ · DOI 10.1016/j.cmet.2019.01.014

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 238–244

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Macrophage culture with serine restriction and metabolite add-back. · source_derived_draft · unverified_draft

## l-serine-macrophage-rescue The limiting branch differs from the nucleotide requirement in dividing T cells. Cell-permeable glutathione, but not formate, rescued IL-1beta mRNA expression under serine restriction in the macrophage experiments. Model: Macrophage culture with serine restriction and metabolite add-back. Limitations: The delivered compound was cell-permeable GSH, not an assumed effect of oral glutathione. Evidence access: Primary abstract Serine Metabolism Supports Macrophage IL-1β Production. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30773464/ · DOI 10.1016/j.cmet.2019.01.014

evidence_access

Primary abstract

experimental_model

Rat-liver CACT proteoliposome assay.

limitations

Does not demonstrate oral glutathione-carnitine synergy.

nutrient_topic

L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine

plain_language

The redox environment can change whether the carrier works.

primary_references

Effect of Copper on the Mitochondrial Carnitine/Acylcarnitine Carrier Via Interaction with Cys136 and Cys155. Possible Implications in Pathophysiology. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32070004/ · DOI 10.3390/molecules25040820

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 146–152

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Rat-liver CACT proteoliposome assay. · source_derived_draft · unverified_draft

## l-carnitine-gsh-carrier The redox environment can change whether the carrier works. Adding reduced glutathione reversed copper inhibition of the reconstituted native rat carnitine-acylcarnitine carrier. Model: Rat-liver CACT proteoliposome assay. Limitations: Does not demonstrate oral glutathione-carnitine synergy. Evidence access: Primary abstract Effect of Copper on the Mitochondrial Carnitine/Acylcarnitine Carrier Via Interaction with Cys136 and Cys155. Possible Implications in Pathophysiology. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32070004/ · DOI 10.3390/molecules25040820

cross_nutrient

Human metal-regulatory transcription factor 1 / MTF1 (human_protein); Mouse metal-regulatory transcription factor 1 / Mtf1 (mouse_protein); Zinc(II) ion (activating_ion)

evidence_span

{"source_cache": "artifacts/zinc-signaling-sources/9507026-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "ecd19e16b15909d46328c2c5dcd9f9536422db7bb12b9dfd9d91763fafe164bd"}

experimental_model

Human and mouse cell extracts and recombinant MTF1

exposure

Zinc versus other tested transition metals; DNA-binding assays. Glutathione was 1 mM in the recombinant-protein cadmium challenge; this is an in-vitro assay concentration.

limitations

In-vitro metal specificity does not mean all cellular metal responses are mediated by direct MTF1 binding.

nutrient_topic

Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc

organism

Homo sapiens; Mus musculus

plain_language

Glutathione helped preserve the zinc-dependent sensor under this chemical stress.

primary_references

[zn-sig-9507026] The DNA binding activity of metal response element-binding transcription factor-1 is activated in vivo and in vitro by zinc, but not by other transition metals. (1998). https://pubmed.ncbi.nlm.nih.gov/9507026/ DOI: 10.1074/jbc.273.12.7127

tissue_or_cell_type

Cell extracts and recombinant protein

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 887–899

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human and mouse cell extracts and recombinant MTF1 · source_derived_draft · unverified_draft

### zn-sig-gsh-mtf1-protection Glutathione protected recombinant MTF1 from cadmium-mediated inactivation, allowing zinc-dependent DNA-binding activity in the assay. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione helped preserve the zinc-dependent sensor under this chemical stress. organism: Homo sapiens; Mus musculus tissue_or_cell_type: Cell extracts and recombinant protein experimental_model: Human and mouse cell extracts and recombinant MTF1 limitations: In-vitro metal specificity does not mean all cellular metal responses are mediated by direct MTF1 binding. exposure: Zinc versus other tested transition metals; DNA-binding assays. Glutathione was 1 mM in the recombinant-protein cadmium challenge; this is an in-vitro assay concentration. cross_nutrient: Human metal-regulatory transcription factor 1 / MTF1 (human_protein); Mouse metal-regulatory transcription factor 1 / Mtf1 (mouse_protein); Zinc(II) ion (activating_ion) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/9507026-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "ecd19e16b15909d46328c2c5dcd9f9536422db7bb12b9dfd9d91763fafe164bd"} [zn-sig-9507026] The DNA binding activity of metal response element-binding transcription factor-1 is activated in vivo and in vitro by zinc, but not by other transition metals. (1998). https://pubmed.ncbi.nlm.nih.gov/9507026/ DOI: 10.1074/jbc.273.12.7127

cross_nutrient

true

evidence_location

Primary abstract; indexed article Introduction/Figure 1

experimental_model

Purified human MMACHC thiol substitution assays

exposure

GSH versus cysteine or homocysteine

limitations

No implication that cysteine availability is irrelevant to cellular GSH synthesis; that upstream pathway was not tested here.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Homo sapiens

plain_language

Having a thiol group was not enough; the enzyme required glutathione in these assays.

primary_references

[kim-2009-gsh-dealkylation] A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins (2009). https://pubmed.ncbi.nlm.nih.gov/19801555/ DOI: 10.1074/jbc.M109.057877

tissue_or_cell_type

Cell-free assay

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 739–751

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human MMACHC thiol substitution assays · source_derived_draft · unverified_draft

### b12-mmachc-thiol-specificity In the human MMACHC dealkylation study, cysteine and homocysteine did not substitute for glutathione as the thiol co-substrate. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Having a thiol group was not enough; the enzyme required glutathione in these assays. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Purified human MMACHC thiol substitution assays limitations: No implication that cysteine availability is irrelevant to cellular GSH synthesis; that upstream pathway was not tested here. exposure: GSH versus cysteine or homocysteine cross_nutrient: true evidence_location: Primary abstract; indexed article Introduction/Figure 1 [kim-2009-gsh-dealkylation] A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins (2009). https://pubmed.ncbi.nlm.nih.gov/19801555/ DOI: 10.1074/jbc.M109.057877

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Purified viral protease; product chromatography, mass spectrometry and quinone staining.

limitations

Cell-free competition does not quantify GSH consumption or establish antiviral benefit in vivo.

nutrient_topic

Myricetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Myricetin

plain_language

A cellular antioxidant can intercept a reaction that inhibits another protein.

primary_references

Food phytochemicals, epigallocatechin gallate and myricetin, covalently bind to the active site of the coronavirus main protease in vitro. · 2021 · https://pubmed.ncbi.nlm.nih.gov/35425933/ · DOI 10.1016/j.arres.2021.100021

trigger_kind

machinery_impairment Imported condition classification; unverified.

Myricetin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 324–330

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified viral protease; product chromatography, mass spectrometry and quinone staining. · source_derived_draft · unverified_draft

## myricetin-mpro-gsh A cellular antioxidant can intercept a reaction that inhibits another protein. Reduced glutathione prevented myricetin–Mpro conjugate formation and canceled the inhibitory effect in the tested assay. Model: Purified viral protease; product chromatography, mass spectrometry and quinone staining. Limitations: Cell-free competition does not quantify GSH consumption or establish antiviral benefit in vivo. Evidence access: Primary full text Food phytochemicals, epigallocatechin gallate and myricetin, covalently bind to the active site of the coronavirus main protease in vitro. · 2021 · https://pubmed.ncbi.nlm.nih.gov/35425933/ · DOI 10.1016/j.arres.2021.100021

evidence_access

Primary abstract

experimental_model

Same biochemical study.

limitations

Context difference from DOPAL chemistry, not a contradiction.

nutrient_topic

Carnosine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnosine / beta-alanyl-L-histidine

plain_language

The preferred scavenger changed with the target molecule.

primary_references

Biochemical characterization of the catecholaldehyde reactivity of L-carnosine and its therapeutic potential in human myocardium. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30191330/ · DOI 10.1007/s00726-018-2647-y

Carnosine: synthesis, transport, carbonyl chemistry and nutrient interactions (2026-09-19) · lines 284–290

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Same biochemical study. · source_derived_draft · unverified_draft

## carnosine-gsh-hne The preferred scavenger changed with the target molecule. Glutathione reacted more readily than carnosine with HNE in the comparative assay. Model: Same biochemical study. Limitations: Context difference from DOPAL chemistry, not a contradiction. Evidence access: Primary abstract Biochemical characterization of the catecholaldehyde reactivity of L-carnosine and its therapeutic potential in human myocardium. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30191330/ · DOI 10.1007/s00726-018-2647-y

cross_nutrient

true

evidence_location

Figure 2A–B; hydroxylation Methods

experimental_model

Recombinant human PHD enzymes; HIF-1 alpha 556–574 peptide hydroxylation detected by VHL/elongin B/C binding

exposure

10 µM FeSO4, 0.5 mM 2-oxoglutarate, pH 7.5, room temperature, 1 h; ascorbate omission/titration and GSH titration; standard ascorbate 2 mM.

limitations

Alternative reductant effects vary with substrate and assay; this is not a nutritional substitution recommendation or proof of in-vivo compensation mechanism.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Homo sapiens proteins

plain_language

These oxygen-sensing enzymes could use support from glutathione when vitamin C was absent in the test tube.

primary_references

[c-reg-nytko] Vitamin C is dispensable for oxygen sensing in vivo. (2011). https://pubmed.ncbi.nlm.nih.gov/21346252/ DOI: 10.1182/blood-2010-09-307637

tissue_or_cell_type

Cell-free

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1145–1157

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PHD enzymes; HIF-1 alpha 556–574 peptide hydroxylation detected by VHL/elongin B/C binding · source_derived_draft · unverified_draft

### c-reg-gsh-substitutes-phd Reduced glutathione stimulated all three tested PHD isoforms in the absence of ascorbate; millimolar GSH could substitute in the peptide assay, indicating reductant redundancy in this setting. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: These oxygen-sensing enzymes could use support from glutathione when vitamin C was absent in the test tube. organism: Homo sapiens proteins tissue_or_cell_type: Cell-free experimental_model: Recombinant human PHD enzymes; HIF-1 alpha 556–574 peptide hydroxylation detected by VHL/elongin B/C binding limitations: Alternative reductant effects vary with substrate and assay; this is not a nutritional substitution recommendation or proof of in-vivo compensation mechanism. exposure: 10 µM FeSO4, 0.5 mM 2-oxoglutarate, pH 7.5, room temperature, 1 h; ascorbate omission/titration and GSH titration; standard ascorbate 2 mM. cross_nutrient: true evidence_location: Figure 2A–B; hydroxylation Methods [c-reg-nytko] Vitamin C is dispensable for oxygen sensing in vivo. (2011). https://pubmed.ncbi.nlm.nih.gov/21346252/ DOI: 10.1182/blood-2010-09-307637

acting_entity

glutathione

dose

SAC IC50 110 micromolar

duration

Time-dependent inhibition; duration not retrieved

evidence_access

Primary abstract

experimental_comparison

SAC and other compounds tested individually; thiol reversal experiments

experimental_model

Purified recombinant squalene monooxygenase assay

interpretation_status

Source-derived research curation; not independent primary verification

limitations

The abstract groups several inhibitors. SAC-specific reversal magnitude and a covalent site are not separately established; dithiols were more effective than monothiols.

nutrient_topic

S-allylcysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · S-allyl-L-cysteine / SAC

organism

Human recombinant protein

plain_language

The enzyme result connects to thiol chemistry.

primary_references

[11385050] Garlic and garlic-derived compounds inhibit human squalene monooxygenase. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11385050/ · DOI 10.1093/jn/131.6.1662

route

Cell-free enzyme assay

tissue_or_cell_type

Purified recombinant squalene monooxygenase assay

S-allylcysteine: sulfur signaling, redox responses and cross-nutrient mechanisms (2026-09-20) · lines 230–237

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified recombinant squalene monooxygenase assay · source_derived_draft · unverified_draft

## s-allylcysteine-sqle-thiol-reversal The enzyme result connects to thiol chemistry. Thiol-containing reagents, including glutathione, prevented or reversed inhibition in the garlic-compound SQLE assay series. Model: Purified recombinant squalene monooxygenase assay Limitations: The abstract groups several inhibitors. SAC-specific reversal magnitude and a covalent site are not separately established; dithiols were more effective than monothiols. Evidence access: Primary abstract [11385050] Garlic and garlic-derived compounds inhibit human squalene monooxygenase. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11385050/ · DOI 10.1093/jn/131.6.1662 Structured context: {"organism": "Human recombinant protein", "tissue_or_cell_type": "Purified recombinant squalene monooxygenase assay", "dose": "SAC IC50 110 micromolar", "duration": "Time-dependent inhibition; duration not retrieved", "route": "Cell-free enzyme assay", "experimental_comparison": "SAC and other compounds tested individually; thiol reversal experiments", "acting_entity": "glutathione", "interpretation_status": "Source-derived research curation; not independent primary verification"}

evidence_span

{"source_cache": "artifacts/glutathione-research/20220146.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c456343cb9386a797d12af2169106d7f3b8033a5fa3882034609d3bbc26ae478", "start_char": 0, "end_char": 1382, "text_sha256": "c456343cb9386a797d12af2169106d7f3b8033a5fa3882034609d3bbc26ae478"}

experimental_model

Inhibited-enzyme crystallography

exposure

GSH and BSO-bound structures

limitations

Binding geometry is species-specific; BSO is an experimental inhibitor, not dietary depletion.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Saccharomyces cerevisiae

plain_language

The product can feed back on its own synthesis.

primary_references

[glutathione-p20220146] Structural basis for feedback and pharmacological inhibition of Saccharomyces cerevisiae glutamate cysteine ligase. (2010). https://pubmed.ncbi.nlm.nih.gov/20220146/ DOI: 10.1074/jbc.m110.104802

tissue_or_cell_type

Purified Gsh1

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 359–370

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inhibited-enzyme crystallography · source_derived_draft · unverified_draft

### glutathione-gcl-feedback-site GSH occupied the glutamate and presumed cysteine sites and disrupted ATP-site Mg coordination in the inhibited yeast structure. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The product can feed back on its own synthesis. organism: Saccharomyces cerevisiae tissue_or_cell_type: Purified Gsh1 experimental_model: Inhibited-enzyme crystallography limitations: Binding geometry is species-specific; BSO is an experimental inhibitor, not dietary depletion. exposure: GSH and BSO-bound structures evidence_span: {"source_cache": "artifacts/glutathione-research/20220146.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c456343cb9386a797d12af2169106d7f3b8033a5fa3882034609d3bbc26ae478", "start_char": 0, "end_char": 1382, "text_sha256": "c456343cb9386a797d12af2169106d7f3b8033a5fa3882034609d3bbc26ae478"} [glutathione-p20220146] Structural basis for feedback and pharmacological inhibition of Saccharomyces cerevisiae glutamate cysteine ligase. (2010). https://pubmed.ncbi.nlm.nih.gov/20220146/ DOI: 10.1074/jbc.m110.104802

evidence_span

{"source_cache": "artifacts/glutathione-research/21029046.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bc7e33127eee3685d1f90bff5a83334d68ac0ee3f73eeb67e4a9e189c5ba20b2", "start_char": 0, "end_char": 1468, "text_sha256": "bc7e33127eee3685d1f90bff5a83334d68ac0ee3f73eeb67e4a9e189c5ba20b2"}

experimental_model

Crystallography, solution oligomers and biochemical assays

exposure

Iron-sulfur/GSH complex and disulfide assays

limitations

The structural cluster complex is not a dietary-iron requirement or proof of supplement synergy.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human GLRX5

plain_language

Glutathione is part of the cluster-binding structure, not only an antioxidant.

primary_references

[glutathione-p21029046] The crystal structure of human GLRX5: iron-sulfur cluster co-ordination, tetrameric assembly and monomer activity. (2011). https://pubmed.ncbi.nlm.nih.gov/21029046/ DOI: 10.1042/bj20101286

tissue_or_cell_type

Purified holo and apo protein

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 788–799

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystallography, solution oligomers and biochemical assays · source_derived_draft · unverified_draft

### glutathione-glrx5-gsh-ligand Each GLRX5-bound [2Fe-2S] cluster was ligated by two protein Cys67 thiols and two GSH cysteine thiols. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione is part of the cluster-binding structure, not only an antioxidant. organism: Human GLRX5 tissue_or_cell_type: Purified holo and apo protein experimental_model: Crystallography, solution oligomers and biochemical assays limitations: The structural cluster complex is not a dietary-iron requirement or proof of supplement synergy. exposure: Iron-sulfur/GSH complex and disulfide assays evidence_span: {"source_cache": "artifacts/glutathione-research/21029046.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bc7e33127eee3685d1f90bff5a83334d68ac0ee3f73eeb67e4a9e189c5ba20b2", "start_char": 0, "end_char": 1468, "text_sha256": "bc7e33127eee3685d1f90bff5a83334d68ac0ee3f73eeb67e4a9e189c5ba20b2"} [glutathione-p21029046] The crystal structure of human GLRX5: iron-sulfur cluster co-ordination, tetrameric assembly and monomer activity. (2011). https://pubmed.ncbi.nlm.nih.gov/21029046/ DOI: 10.1042/bj20101286

evidence_span

{"source_cache": "artifacts/glutathione-research/6424115.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08", "start_char": 0, "end_char": 1307, "text_sha256": "8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08"}

experimental_model

Enzyme oxidation and radiolabeled binding assays

exposure

NAPQI or acetaminophen with reductants

limitations

Experimental chemistry; no new human dose threshold or treatment regimen is inferred.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Mouse microsomes and cell-free cytochrome-P450 system

plain_language

Glutathione diverted the reactive metabolite into a conjugate.

primary_references

[glutathione-p6424115] N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. (1984). https://pubmed.ncbi.nlm.nih.gov/6424115/ DOI: 10.1073/pnas.81.5.1327

tissue_or_cell_type

Acetaminophen reactive-metabolite handling

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1035–1046

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme oxidation and radiolabeled binding assays · source_derived_draft · unverified_draft

### glutathione-napqi-conjugation Adding GSH decreased covalent microsomal protein binding while forming 3-S-glutathionylacetaminophen. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione diverted the reactive metabolite into a conjugate. organism: Mouse microsomes and cell-free cytochrome-P450 system tissue_or_cell_type: Acetaminophen reactive-metabolite handling experimental_model: Enzyme oxidation and radiolabeled binding assays limitations: Experimental chemistry; no new human dose threshold or treatment regimen is inferred. exposure: NAPQI or acetaminophen with reductants evidence_span: {"source_cache": "artifacts/glutathione-research/6424115.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08", "start_char": 0, "end_char": 1307, "text_sha256": "8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08"} [glutathione-p6424115] N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. (1984). https://pubmed.ncbi.nlm.nih.gov/6424115/ DOI: 10.1073/pnas.81.5.1327

evidence_span

{"source_cache": "artifacts/iron-research/24439385.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703", "start_char": 0, "end_char": 957, "text_sha256": "f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703"}

experimental_model

Metabolomics, chemoproteomics, perturbation and cancer-cell sensitivity profiling

exposure

Two classes of ferroptosis-inducing compounds

limitations

Preclinical drug-response mechanism; selenium or vitamin E supplementation is not established as a universal treatment.

nutrient_topic

Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron

organism

Human cancer-cell lines and mouse xenografts

plain_language

Losing the antioxidant substrate and directly blocking its enzyme are different routes into the same vulnerability.

primary_references

[iron-p24439385] Regulation of ferroptotic cancer cell death by GPX4. (2014). https://pubmed.ncbi.nlm.nih.gov/24439385/ DOI: 10.1016/j.cell.2013.12.010

tissue_or_cell_type

Glutathione/GPX4 antioxidant system

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1252–1263

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolomics, chemoproteomics, perturbation and cancer-cell sensitivity profiling · source_derived_draft · unverified_draft

### iron-gsh-gpx-loss Glutathione depletion in response to one class of ferroptosis inducers inactivated glutathione peroxidases, while another class directly inhibited GPX4. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Losing the antioxidant substrate and directly blocking its enzyme are different routes into the same vulnerability. organism: Human cancer-cell lines and mouse xenografts tissue_or_cell_type: Glutathione/GPX4 antioxidant system experimental_model: Metabolomics, chemoproteomics, perturbation and cancer-cell sensitivity profiling limitations: Preclinical drug-response mechanism; selenium or vitamin E supplementation is not established as a universal treatment. exposure: Two classes of ferroptosis-inducing compounds evidence_span: {"source_cache": "artifacts/iron-research/24439385.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703", "start_char": 0, "end_char": 957, "text_sha256": "f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703"} [iron-p24439385] Regulation of ferroptotic cancer cell death by GPX4. (2014). https://pubmed.ncbi.nlm.nih.gov/24439385/ DOI: 10.1016/j.cell.2013.12.010

cell_type

Dendritic cells and T cells

experimental_model

Mouse DC/T-cell cocultures

limitations

Distinct from an unproven secreted TrxR1 circuit; not the sole established route in humans.

organism

Mus musculus

Selenium: literature corrections and mechanism additions · lines 1312–1322

Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Mouse DC/T-cell cocultures · secondary_verified · secondary_verified

## dc-gsh-cysteine Dendritic cells can supply cysteine by exporting and breaking down glutathione. Dendritic-cell GSH secretion followed by extracellular cleavage contributes extracellular cysteine in mouse DC/T-cell coculture. Organism: Mus musculus Cell type: Dendritic cells and T cells Experimental model: Mouse DC/T-cell cocultures Limitations: Distinct from an unproven secreted TrxR1 circuit; not the sole established route in humans. Primary reference: [Extracellular redox modulation by regulatory T cells](https://pmc.ncbi.nlm.nih.gov/articles/PMC2760945/)

cross_nutrient

B6-dependent transsulfuration connects methionine/homocysteine to the cysteine supply for glutathione.

experimental_model

Cultured human hepatoma cell line; metabolic sulfur tracing

limitations

Fraction is culture-specific and traces sulfur, not all glutathione atoms; this experiment did not measure dietary B6 depletion.

nutrient_topic

Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6

organism

Homo sapiens

plain_language

In this cell system, sulfur routed through B6-dependent enzymes helped supply glutathione.

primary_references

[b6-glutathione-2000] The quantitatively important relationship between homocysteine metabolism and glutathione synthesis by the transsulfuration pathway and its regulation by redox changes (2000). https://pubmed.ncbi.nlm.nih.gov/11041866/ DOI: 10.1021/bi001088w

tissue_or_cell_type

Cultured human hepatoma cell line

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 590–600

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cultured human hepatoma cell line; metabolic sulfur tracing · source_derived_draft · unverified_draft

### b6-met-transsulfuration-glutathione Tracing in a cultured human hepatoma cell line estimated that transsulfuration supplied homocysteine-derived sulfur to approximately half of the intracellular glutathione pool. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this cell system, sulfur routed through B6-dependent enzymes helped supply glutathione. organism: Homo sapiens tissue_or_cell_type: Cultured human hepatoma cell line experimental_model: Cultured human hepatoma cell line; metabolic sulfur tracing limitations: Fraction is culture-specific and traces sulfur, not all glutathione atoms; this experiment did not measure dietary B6 depletion. cross_nutrient: B6-dependent transsulfuration connects methionine/homocysteine to the cysteine supply for glutathione. [b6-glutathione-2000] The quantitatively important relationship between homocysteine metabolism and glutathione synthesis by the transsulfuration pathway and its regulation by redox changes (2000). https://pubmed.ncbi.nlm.nih.gov/11041866/ DOI: 10.1021/bi001088w

evidence_access

Primary abstract

experimental_model

Mouse liver dosing study.

limitations

Not evidence of universal human glutathione depletion.

nutrient_topic

Luteolin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Luteolin / 3′,4′,5,7-tetrahydroxyflavone

plain_language

An antioxidant-associated compound can lower this defense system in a particular model.

primary_references

Luteolin inhibits the Nrf2 signaling pathway and tumor growth in vivo. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24747074/ · DOI 10.1016/j.bbrc.2014.04.039

Luteolin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 452–458

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse liver dosing study. · source_derived_draft · unverified_draft

## luteolin-mouse-nrf2-gsh An antioxidant-associated compound can lower this defense system in a particular model. Luteolin reduced liver glutathione and antioxidant-enzyme expression in wild-type mice under basal and BHA-induced conditions. Model: Mouse liver dosing study. Limitations: Not evidence of universal human glutathione depletion. Evidence access: Primary abstract Luteolin inhibits the Nrf2 signaling pathway and tumor growth in vivo. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24747074/ · DOI 10.1016/j.bbrc.2014.04.039

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Wild-type versus Nrf2-null mice.

limitations

Knockout context does not define a dietary deficiency.

nutrient_topic

Luteolin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Luteolin / 3′,4′,5,7-tetrahydroxyflavone

plain_language

Removing the regulator changed the response to the compound.

primary_references

Luteolin inhibits the Nrf2 signaling pathway and tumor growth in vivo. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24747074/ · DOI 10.1016/j.bbrc.2014.04.039

trigger_kind

machinery_impairment Imported condition classification; unverified.

Luteolin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 460–466

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Wild-type versus Nrf2-null mice. · source_derived_draft · unverified_draft

## luteolin-mouse-nrf2-loss Removing the regulator changed the response to the compound. The distinct luteolin-associated liver responses were absent in Nrf2-knockout mice. Model: Wild-type versus Nrf2-null mice. Limitations: Knockout context does not define a dietary deficiency. Evidence access: Primary abstract Luteolin inhibits the Nrf2 signaling pathway and tumor growth in vivo. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24747074/ · DOI 10.1016/j.bbrc.2014.04.039

evidence_access

Primary abstract

experimental_model

Cell-free chemistry; exposure concentration and duration unavailable in the accessed abstract.

limitations

Physical interaction is not a quantified in-vivo detoxification rate or human glutathione-depletion threshold.

nutrient_topic

Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins

plain_language

Glutathione can interact with the compound before a downstream signal is measured.

primary_references

Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 108–114

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free chemistry; exposure concentration and duration unavailable in the accessed abstract. · source_derived_draft · unverified_draft

## cucurbitacin-b-gsh-interaction Glutathione can interact with the compound before a downstream signal is measured. UV spectroscopy and FTICR mass spectrometry detected physical interaction between cucurbitacin B and glutathione in a cell-free system. Model: Cell-free chemistry; exposure concentration and duration unavailable in the accessed abstract. Limitations: Physical interaction is not a quantified in-vivo detoxification rate or human glutathione-depletion threshold. Evidence access: Primary abstract Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Patient fibroblasts, biosynthesis inhibition and mouse genetics

exposure

Genetic or pharmacological CoQ depletion and in-vitro repletion

limitations

Tissue-specific disease models; mouse residual percentages are not diagnostic human thresholds.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

Human fibroblasts/HeLa cells and Pdss2 mutant mice

plain_language

The CoQ defect connected to another antioxidant pool in this kidney model.

primary_references

[coq10-p27856618] Coenzyme Q deficiency causes impairment of the sulfide oxidation pathway. (2017). https://pubmed.ncbi.nlm.nih.gov/27856618/ DOI: 10.15252/emmm.201606356

tissue_or_cell_type

Sulfide oxidation and tissue CoQ

trigger_kind

machinery_impairment Imported condition classification; unverified.

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 580–591

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient fibroblasts, biosynthesis inhibition and mouse genetics · source_derived_draft · unverified_draft

### coq10-kidney-glutathione Pdss2-mutant kidneys had glutathione depletion, whereas the less CoQ-depleted brain lacked these abnormalities. Condition category: machinery_impairment nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The CoQ defect connected to another antioxidant pool in this kidney model. organism: Human fibroblasts/HeLa cells and Pdss2 mutant mice tissue_or_cell_type: Sulfide oxidation and tissue CoQ experimental_model: Patient fibroblasts, biosynthesis inhibition and mouse genetics limitations: Tissue-specific disease models; mouse residual percentages are not diagnostic human thresholds. exposure: Genetic or pharmacological CoQ depletion and in-vitro repletion evidence_span: {"source_cache": "artifacts/coq10-research/27856618.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8b98767d3bed9661c05c7b82b55817b6d9912abd8bfc9dd9d59ca9763025485", "start_char": 0, "end_char": 1261, "text_sha256": "a8b98767d3bed9661c05c7b82b55817b6d9912abd8bfc9dd9d59ca9763025485"} [coq10-p27856618] Coenzyme Q deficiency causes impairment of the sulfide oxidation pathway. (2017). https://pubmed.ncbi.nlm.nih.gov/27856618/ DOI: 10.15252/emmm.201606356

evidence_span

{"source_cache": "artifacts/sulforaphane-research/30581542.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77cf6674cf9b9bc140a228588a53c937966fd3a67397c1c4970221c5cc58a0b1", "start_char": 923, "end_char": 1092, "text_sha256": "bed9ef1323b513b1e31b65277f28b935ddf0c9b0c83cbe9ee9f827f97806846c"}

experimental_model

Human enzyme mutagenesis, kinetics and molecular dynamics

exposure

S-loop variants; established biosynthetic reactions described in the introduction

limitations

Reaction descriptions are background chemistry in a primary enzyme paper, not evidence that sulforaphane corrects inherited GSS deficiency.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human GSS

plain_language

A second enzyme, glycine and energy complete the molecule.

primary_references

[sulforaphane-p30581542] Genetic Mutations in the S-loop of Human Glutathione Synthetase: Links Between Substrate Binding, Active Site Structure and Allostery. (2019). https://pubmed.ncbi.nlm.nih.gov/30581542/ DOI: 10.1016/j.csbj.2018.11.008

tissue_or_cell_type

Glutathione synthesis and substrate binding

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 853–864

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human enzyme mutagenesis, kinetics and molecular dynamics · source_derived_draft · unverified_draft

### sulforaphane-gss-second-step Human GSS joins gamma-glutamylcysteine and glycine in an ATP-dependent reaction to form glutathione. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second enzyme, glycine and energy complete the molecule. organism: Human GSS tissue_or_cell_type: Glutathione synthesis and substrate binding experimental_model: Human enzyme mutagenesis, kinetics and molecular dynamics limitations: Reaction descriptions are background chemistry in a primary enzyme paper, not evidence that sulforaphane corrects inherited GSS deficiency. exposure: S-loop variants; established biosynthetic reactions described in the introduction evidence_span: {"source_cache": "artifacts/sulforaphane-research/30581542.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77cf6674cf9b9bc140a228588a53c937966fd3a67397c1c4970221c5cc58a0b1", "start_char": 923, "end_char": 1092, "text_sha256": "bed9ef1323b513b1e31b65277f28b935ddf0c9b0c83cbe9ee9f827f97806846c"} [sulforaphane-p30581542] Genetic Mutations in the S-loop of Human Glutathione Synthetase: Links Between Substrate Binding, Active Site Structure and Allostery. (2019). https://pubmed.ncbi.nlm.nih.gov/30581542/ DOI: 10.1016/j.csbj.2018.11.008

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_location

Abstract; Figure 1B

evidence_span

No significant changes in GSH concentration

experimental_model

Male Sprague-Dawley rats, eight weeks old; thiamine-deficient chow plus daily pyrithiamine 0.25 mg/kg intraperitoneally; pair-fed thiamine-injected controls; days 13 and 14 brain assays.

exposure

Thiamine-deficient chow plus pyrithiamine, day 14 with seizures and absent righting reflex

limitations

Total regional concentration does not measure glutathione turnover or subcellular redox state; no direct NADPH result is inferred.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Rattus norvegicus

plain_language

Higher oxidant signals did not require a detectable fall in the measured glutathione pool.

primary_references

[langlais-1997-brain-oxidants] Increased cerebral free radical production during thiamine deficiency (1997). https://pubmed.ncbi.nlm.nih.gov/9203158/ DOI: 10.1007/BF02674735

tissue_or_cell_type

Thalamus and cortex

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1169–1181

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Male Sprague-Dawley rats, eight weeks old; thiamine-deficient chow plus daily pyrithiamine 0.25 mg/kg intraperitoneally; pair-fed thiamine-injected controls; days 13 and 14 brain assays. · source_derived_draft · unverified_draft

### thiamine-def-glutathione-preserved-oxidant-context Reduced glutathione concentrations did not change significantly in thalamus or cortex on days 13 or 14. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Higher oxidant signals did not require a detectable fall in the measured glutathione pool. organism: Rattus norvegicus tissue_or_cell_type: Thalamus and cortex experimental_model: Male Sprague-Dawley rats, eight weeks old; thiamine-deficient chow plus daily pyrithiamine 0.25 mg/kg intraperitoneally; pair-fed thiamine-injected controls; days 13 and 14 brain assays. limitations: Total regional concentration does not measure glutathione turnover or subcellular redox state; no direct NADPH result is inferred. evidence_location: Abstract; Figure 1B evidence_span: No significant changes in GSH concentration exposure: Thiamine-deficient chow plus pyrithiamine, day 14 with seizures and absent righting reflex [langlais-1997-brain-oxidants] Increased cerebral free radical production during thiamine deficiency (1997). https://pubmed.ncbi.nlm.nih.gov/9203158/ DOI: 10.1007/BF02674735

experimental_model

Purified biochemical reaction; GSH measured by amperometric titration.

exposure_category

Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.

limitations

No demonstration that ordinary KI intake depletes human glutathione.

nutrient_topic

Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide

plain_language

This iodine chemistry can consume glutathione in a test system.

primary_references

Free radical generation and coupled thiol oxidation by lactoperoxidase/SCN-/H2O2. · 1992 · https://pubmed.ncbi.nlm.nih.gov/1324202/ · DOI 10.1016/0891-5849(92)90014-8

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 248–254

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · Purified biochemical reaction; GSH measured by amperometric titration. · source_derived_draft · unverified_draft

## ki-gsh This iodine chemistry can consume glutathione in a test system. Iodide substituted for thiocyanate in LPO/H2O2-dependent glutathione oxidation; chloride and bromide were ineffective substitutes. Model: Purified biochemical reaction; GSH measured by amperometric titration. Limitations: No demonstration that ordinary KI intake depletes human glutathione. Evidence location: Primary abstract Free radical generation and coupled thiol oxidation by lactoperoxidase/SCN-/H2O2. · 1992 · https://pubmed.ncbi.nlm.nih.gov/1324202/ · DOI 10.1016/0891-5849(92)90014-8

evidence_access

Primary full text

experimental_model

Human cells; 0.5 mM CuSO4, up to 10 micrograms/mL myricetin.

limitations

Do not convert proposed thiol chemistry into measured GSH depletion.

nutrient_topic

Myricetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Myricetin

plain_language

More injury did not require a further measured fall in glutathione.

primary_references

Neurotoxic Effect of Flavonol Myricetin in the Presence of Excess Copper. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33562817/ · DOI 10.3390/molecules26040845

Myricetin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 356–362

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cells; 0.5 mM CuSO4, up to 10 micrograms/mL myricetin. · source_derived_draft · unverified_draft

## myricetin-copper-gsh-null More injury did not require a further measured fall in glutathione. Myricetin did not further reduce the glutathione pool already lowered by copper in this SH-SY5Y experiment. Model: Human cells; 0.5 mM CuSO4, up to 10 micrograms/mL myricetin. Limitations: Do not convert proposed thiol chemistry into measured GSH depletion. Evidence access: Primary full text Neurotoxic Effect of Flavonol Myricetin in the Presence of Excess Copper. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33562817/ · DOI 10.3390/molecules26040845

evidence_access

Primary full text

experimental_model

Human A549/HT1080 experiments; polyamine panel.

limitations

Does not negate GSH protection or generalize to every dose and cell type.

nutrient_topic

Spermidine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Spermidine

plain_language

Iron-dependent injury did not require measured glutathione depletion.

primary_references

Polyamine-mediated ferroptosis amplification acts as a targetable vulnerability in cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38504107/ · DOI 10.1038/s41467-024-46776-w

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 542–548

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human A549/HT1080 experiments; polyamine panel. · source_derived_draft · unverified_draft

## spermidine-ferroptosis-gsh-null Iron-dependent injury did not require measured glutathione depletion. Polyamine treatment did not deplete cellular glutathione in the reported comparison. Model: Human A549/HT1080 experiments; polyamine panel. Limitations: Does not negate GSH protection or generalize to every dose and cell type. Evidence access: Primary full text Polyamine-mediated ferroptosis amplification acts as a targetable vulnerability in cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38504107/ · DOI 10.1038/s41467-024-46776-w

evidence_access

Primary abstract

experimental_model

Human crossover trial with one-week washout.

limitations

Blood abundance is not synthesis flux, tissue sufficiency or evidence that selenium, B6 or glutathione supplementation adds benefit.

nutrient_topic

Astaxanthin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Astaxanthin

plain_language

A glutathione measurement improved without a corresponding exercise-fuel effect.

primary_references

Astaxanthin Supplementation Increases Glutathione Concentrations but Does Not Impact Fat Oxidation During Exercise in Active Young Men. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34611051/ · DOI 10.1123/ijsnem.2021-0138

Astaxanthin: transport, membrane chemistry, signaling and nutrient interactions (2026-09-19) · lines 446–452

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human crossover trial with one-week washout. · source_derived_draft · unverified_draft

## astaxanthin-glutathione-human A glutathione measurement improved without a corresponding exercise-fuel effect. In 14 active young men, 6 mg/day for four weeks increased whole-blood glutathione by approximately 7%, while fat oxidation, hydrogen peroxide and malondialdehyde did not change. Model: Human crossover trial with one-week washout. Limitations: Blood abundance is not synthesis flux, tissue sufficiency or evidence that selenium, B6 or glutathione supplementation adds benefit. Evidence access: Primary abstract Astaxanthin Supplementation Increases Glutathione Concentrations but Does Not Impact Fat Oxidation During Exercise in Active Young Men. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34611051/ · DOI 10.1123/ijsnem.2021-0138

evidence_access

Primary abstract

experimental_model

Human-cell GLS2/p53 and oxidative-stress experiments.

limitations

Cysteine, glycine and synthesis machinery remain necessary; glutamate is not established as the universal limiting substrate.

nutrient_topic

L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate

plain_language

The same supply route fed antioxidant chemistry as well as energy metabolism.

primary_references

Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20378837/ · DOI 10.1073/pnas.1001006107

L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 226–232

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human-cell GLS2/p53 and oxidative-stress experiments. · source_derived_draft · unverified_draft

## glutamate-gls2-gsh The same supply route fed antioxidant chemistry as well as energy metabolism. Increasing GLS2 supported higher reduced-glutathione levels, lower reactive oxygen species and protection from peroxide-induced apoptosis in the reported cell experiments. Model: Human-cell GLS2/p53 and oxidative-stress experiments. Limitations: Cysteine, glycine and synthesis machinery remain necessary; glutamate is not established as the universal limiting substrate. Evidence access: Primary abstract Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20378837/ · DOI 10.1073/pnas.1001006107

evidence_span

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experimental_model

Purified mammalian enzymes and expression comparison

exposure

CHAC1/CHAC2 substrate and kinetics comparison

limitations

Human kinetics and yeast structure are distinct; this does not establish a universal turnover rate in vivo.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human and mouse enzymes; yeast structural homolog

plain_language

A separate enzyme supports slower glutathione turnover.

primary_references

[glutathione-p27913623] ChaC2, an Enzyme for Slow Turnover of Cytosolic Glutathione. (2017). https://pubmed.ncbi.nlm.nih.gov/27913623/ DOI: 10.1074/jbc.m116.727479

tissue_or_cell_type

Cytosolic glutathione turnover

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 593–604

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified mammalian enzymes and expression comparison · source_derived_draft · unverified_draft

### glutathione-chac2-gsh Purified human CHAC2 degraded reduced GSH with lower catalytic efficiency than CHAC1. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separate enzyme supports slower glutathione turnover. organism: Human and mouse enzymes; yeast structural homolog tissue_or_cell_type: Cytosolic glutathione turnover experimental_model: Purified mammalian enzymes and expression comparison limitations: Human kinetics and yeast structure are distinct; this does not establish a universal turnover rate in vivo. exposure: CHAC1/CHAC2 substrate and kinetics comparison evidence_span: {"source_cache": "artifacts/glutathione-research/27913623.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ddf397c2cb8fd60423c89cab28a0b54d124f0e34e0564a32d6bca36841530694", "start_char": 0, "end_char": 1617, "text_sha256": "ddf397c2cb8fd60423c89cab28a0b54d124f0e34e0564a32d6bca36841530694"} [glutathione-p27913623] ChaC2, an Enzyme for Slow Turnover of Cytosolic Glutathione. (2017). https://pubmed.ncbi.nlm.nih.gov/27913623/ DOI: 10.1074/jbc.m116.727479

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Sulfite/thiosulfate incubation of rat cortical slices and cell-free GSSG

exposure

One- versus three-hour incubations; 10 micromolar sulfite redox observations

limitations

Concentration, duration and preparation matter; GPx activity is not evidence of selenium depletion.

nutrient_topic

Molybdenum research collection; topical membership is not evidence of a direct dietary effect. · Molybdenum

organism

Rattus norvegicus; cell-free comparison

plain_language

The antioxidant pool changed in this tissue experiment.

primary_references

[mo-p25777939] In vitro evidence that sulfite impairs glutamatergic neurotransmission and inhibits glutathione metabolism-related enzymes in rat cerebral cortex. (2015). https://pubmed.ncbi.nlm.nih.gov/25777939/ DOI: 10.1016/j.ijdevneu.2015.03.005

tissue_or_cell_type

Cerebral cortex

trigger_kind

machinery_impairment Imported condition classification; unverified.

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 1405–1416

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Sulfite/thiosulfate incubation of rat cortical slices and cell-free GSSG · source_derived_draft · unverified_draft

### mo-sulfite-gsh At 10 micromolar, sulfite lowered glutathione and increased lipid-peroxidation markers after one hour. Condition category: machinery_impairment nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: The antioxidant pool changed in this tissue experiment. organism: Rattus norvegicus; cell-free comparison tissue_or_cell_type: Cerebral cortex experimental_model: Sulfite/thiosulfate incubation of rat cortical slices and cell-free GSSG limitations: Concentration, duration and preparation matter; GPx activity is not evidence of selenium depletion. exposure: One- versus three-hour incubations; 10 micromolar sulfite redox observations evidence_span: {"source_cache": "artifacts/molybdenum-research/25777939.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1768480178724867d4c7a98f723cfd1a0010f7973eae4a4baea3d1261a06fdd2", "start_char": 0, "end_char": 2017, "text_sha256": "1768480178724867d4c7a98f723cfd1a0010f7973eae4a4baea3d1261a06fdd2"} [mo-p25777939] In vitro evidence that sulfite impairs glutamatergic neurotransmission and inhibits glutathione metabolism-related enzymes in rat cerebral cortex. (2015). https://pubmed.ncbi.nlm.nih.gov/25777939/ DOI: 10.1016/j.ijdevneu.2015.03.005

evidence_span

{"source_cache": "artifacts/nasunin-research/bone2016.publisher-abstract.txt", "locator": "Primary publisher abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "83d6dc95bb4cccd5028a3908a5a44639274f59f18e1cea4b13f6133b9fe726dc", "start_char": 0, "end_char": 1187, "text_sha256": "83d6dc95bb4cccd5028a3908a5a44639274f59f18e1cea4b13f6133b9fe726dc"}

experimental_model

Oxidant-challenged osteoblast-like cells with pharmacological pathway inhibition

exposure

Purified trans-nasunin pretreatment 0.1 nM-1 micromolar; t-BHP 250 micromolar for 3 h; redox/function experiments at 1 nM

limitations

Cell-line protection does not establish bone-density or fracture benefits in humans. PI3K inhibition supports pathway involvement, not direct nasunin binding.

nutrient_topic

Nasunin research collection; topical membership is not evidence of a direct dietary effect. · Nasunin

organism

Mouse MC3T3-E1 cells

plain_language

The response includes a molecule shared with several nutrient-dependent defenses.

primary_references

[nasunin-pbone2016] Nasunin, a new player in the field of osteoblast protection against oxidative stress (2016). https://air.unimi.it/handle/2434/378237 DOI: 10.1016/j.jff.2016.03.007

tissue_or_cell_type

Survival, differentiation markers, redox state and Akt signaling

Nasunin: identity, redox chemistry and nutrient connections (2026-09-17) · lines 328–339

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oxidant-challenged osteoblast-like cells with pharmacological pathway inhibition · source_derived_draft · unverified_draft

### nasunin-bone-gsh At 1 nM, nasunin increased intracellular glutathione in challenged cells. Condition category: normal nutrient_topic: Nasunin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response includes a molecule shared with several nutrient-dependent defenses. organism: Mouse MC3T3-E1 cells tissue_or_cell_type: Survival, differentiation markers, redox state and Akt signaling experimental_model: Oxidant-challenged osteoblast-like cells with pharmacological pathway inhibition limitations: Cell-line protection does not establish bone-density or fracture benefits in humans. PI3K inhibition supports pathway involvement, not direct nasunin binding. exposure: Purified trans-nasunin pretreatment 0.1 nM-1 micromolar; t-BHP 250 micromolar for 3 h; redox/function experiments at 1 nM evidence_span: {"source_cache": "artifacts/nasunin-research/bone2016.publisher-abstract.txt", "locator": "Primary publisher abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "83d6dc95bb4cccd5028a3908a5a44639274f59f18e1cea4b13f6133b9fe726dc", "start_char": 0, "end_char": 1187, "text_sha256": "83d6dc95bb4cccd5028a3908a5a44639274f59f18e1cea4b13f6133b9fe726dc"} [nasunin-pbone2016] Nasunin, a new player in the field of osteoblast protection against oxidative stress (2016). https://air.unimi.it/handle/2434/378237 DOI: 10.1016/j.jff.2016.03.007

evidence_access

Primary abstract

experimental_model

Biochemical kinetic and mass-spectrometric studies.

limitations

Adduct formation is not proof of systemic glutathione depletion.

nutrient_topic

CLA collection; isomer, preparation, species, exposure and manipulation remain explicit. · Conjugated linoleic acid / CLA isomer family

plain_language

Glutathione can temporarily bind a CLA-derived metabolite.

primary_references

The Chemical Basis of Thiol Addition to Nitro-conjugated Linoleic Acid, a Protective Cell-signaling Lipid. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27923813/ · DOI 10.1074/jbc.M116.756288

Conjugated linoleic acid: isomers, signaling, nutrient interactions and discovery (2026-09-19) · lines 342–348

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Biochemical kinetic and mass-spectrometric studies. · source_derived_draft · unverified_draft

## cla-gsh-adduct Glutathione can temporarily bind a CLA-derived metabolite. NO2-CLA reacted reversibly with glutathione and other low-molecular-weight thiols through electrophilic beta and delta carbons. Model: Biochemical kinetic and mass-spectrometric studies. Limitations: Adduct formation is not proof of systemic glutathione depletion. Evidence access: Primary abstract The Chemical Basis of Thiol Addition to Nitro-conjugated Linoleic Acid, a Protective Cell-signaling Lipid. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27923813/ · DOI 10.1074/jbc.M116.756288

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/biotin-research/34818536.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "48bcb3951c9b630862fdda839e0a54b80abe9e2cf2e79d0bfb7547e2af317523", "start_char": 35800, "end_char": 36138, "text_sha256": "b1dd7e5022ba64d19114d853d2f75c43e061cdca76e1938e95c19379e96c3933"}

experimental_model

Primary human-islet tracer metabolomics and PC knockdown under inflammatory/nitrosative stress

exposure

Glucose tracer, PC knockdown and nitric-oxide donor exposure

limitations

Genetic perturbation of PC in isolated islets is not dietary biotin depletion or evidence that biotin supplements raise glutathione in replete people.

nutrient_topic

Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin

organism

Homo sapiens

plain_language

PC connects carbon metabolism to the cell’s ability to maintain glutathione.

primary_references

[b7-p34818536] Glucose metabolism and pyruvate carboxylase enhance glutathione synthesis and restrict oxidative stress in pancreatic islets. (2021). https://pubmed.ncbi.nlm.nih.gov/34818536/ DOI: 10.1016/j.celrep.2021.110037

tissue_or_cell_type

Primary human pancreatic islets

trigger_kind

machinery_impairment Imported condition classification; unverified.

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 871–882

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary human-islet tracer metabolomics and PC knockdown under inflammatory/nitrosative stress · source_derived_draft · unverified_draft

### b7-pc-islet-gsh Genetic depletion of PC in human islets reduced glutathione and the GSH/GSSG ratio under nitrosative stress. Condition category: machinery_impairment nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: PC connects carbon metabolism to the cell’s ability to maintain glutathione. organism: Homo sapiens tissue_or_cell_type: Primary human pancreatic islets experimental_model: Primary human-islet tracer metabolomics and PC knockdown under inflammatory/nitrosative stress limitations: Genetic perturbation of PC in isolated islets is not dietary biotin depletion or evidence that biotin supplements raise glutathione in replete people. exposure: Glucose tracer, PC knockdown and nitric-oxide donor exposure evidence_span: {"source_cache": "artifacts/biotin-research/34818536.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "48bcb3951c9b630862fdda839e0a54b80abe9e2cf2e79d0bfb7547e2af317523", "start_char": 35800, "end_char": 36138, "text_sha256": "b1dd7e5022ba64d19114d853d2f75c43e061cdca76e1938e95c19379e96c3933"} [b7-p34818536] Glucose metabolism and pyruvate carboxylase enhance glutathione synthesis and restrict oxidative stress in pancreatic islets. (2021). https://pubmed.ncbi.nlm.nih.gov/34818536/ DOI: 10.1016/j.celrep.2021.110037

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/biotin-research/31006591.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0dcedbfac623863bd4ae86ed1bb97cef0ef56bd417bd0d49507ef47d16af7b4e", "start_char": 0, "end_char": 1141, "text_sha256": "0dcedbfac623863bd4ae86ed1bb97cef0ef56bd417bd0d49507ef47d16af7b4e"}

experimental_model

Liver-specific Pcx-knockout mice

exposure

Genetic deletion of hepatic pyruvate carboxylase

limitations

Genetic enzyme deletion is not a dietary biotin experiment. Cross-nutrient implications identify pathway dependence rather than a proven supplement response.

nutrient_topic

Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin

organism

Mus musculus

plain_language

The consequences can reach antioxidant supply, not just fuel production.

primary_references

[b7-p31006591] Pyruvate-Carboxylase-Mediated Anaplerosis Promotes Antioxidant Capacity by Sustaining TCA Cycle and Redox Metabolism in Liver. (2019). https://pubmed.ncbi.nlm.nih.gov/31006591/ DOI: 10.1016/j.cmet.2019.03.014

tissue_or_cell_type

Liver and systemic metabolism

trigger_kind

machinery_impairment Imported condition classification; unverified.

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 845–856

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Liver-specific Pcx-knockout mice · source_derived_draft · unverified_draft

### b7-pc-null-glutathione Liver-specific Pcx deletion depleted hepatic glutathione and was associated with greater oxidative stress and inflammation. Condition category: machinery_impairment nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The consequences can reach antioxidant supply, not just fuel production. organism: Mus musculus tissue_or_cell_type: Liver and systemic metabolism experimental_model: Liver-specific Pcx-knockout mice limitations: Genetic enzyme deletion is not a dietary biotin experiment. Cross-nutrient implications identify pathway dependence rather than a proven supplement response. exposure: Genetic deletion of hepatic pyruvate carboxylase evidence_span: {"source_cache": "artifacts/biotin-research/31006591.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0dcedbfac623863bd4ae86ed1bb97cef0ef56bd417bd0d49507ef47d16af7b4e", "start_char": 0, "end_char": 1141, "text_sha256": "0dcedbfac623863bd4ae86ed1bb97cef0ef56bd417bd0d49507ef47d16af7b4e"} [b7-p31006591] Pyruvate-Carboxylase-Mediated Anaplerosis Promotes Antioxidant Capacity by Sustaining TCA Cycle and Redox Metabolism in Liver. (2019). https://pubmed.ncbi.nlm.nih.gov/31006591/ DOI: 10.1016/j.cmet.2019.03.014

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse BAT carrier-loss and isotope/metabolite experiments.

limitations

Does not establish isoleucine supplementation as a glutathione intervention; the traced amino acids and cell context remain explicit.

nutrient_topic

L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine

plain_language

Transport and nitrogen handling can affect antioxidant production.

primary_references

BCAA-nitrogen flux in brown fat controls metabolic health independent of thermogenesis. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38653240/ · DOI 10.1016/j.cell.2024.03.030

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 90–96

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse BAT carrier-loss and isotope/metabolite experiments. · source_derived_draft · unverified_draft

## isoleucine-bcaa-glutathione Transport and nitrogen handling can affect antioxidant production. Impaired mitochondrial BCAA nitrogen flux reduced synthesis of downstream metabolites including glutathione and increased oxidative stress in the tested BAT system. Model: Mouse BAT carrier-loss and isotope/metabolite experiments. Limitations: Does not establish isoleucine supplementation as a glutathione intervention; the traced amino acids and cell context remain explicit. Evidence access: Primary full text BCAA-nitrogen flux in brown fat controls metabolic health independent of thermogenesis. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38653240/ · DOI 10.1016/j.cell.2024.03.030

dose

Chemically profiled ME-D hot-soup or freeze-dried preparation

duration

Acute cell exposure and study-specified mouse dosing

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human BEAS-2B cells and orally dosed mice

limitations

The preparation contained moringin, glucomoringin and polyphenols, so the response cannot be assigned to one constituent or treated as a human clinical outcome.

nutrient_topic

Moringa oleifera chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Moringa oleifera

organism

Human BEAS-2B cells and orally dosed mice

plain_language

The standardized multi-constituent ME-D leaf preparation increased NRF2-regulated NQO1 and HMOX1 expression and cellular glutathione in BEAS-2B cells, and increased NRF2-regulated genes after oral dosing in mice.

primary_references

Development of Moringa oleifera as functional food targeting NRF2 signaling: antioxidant and anti-inflammatory activity in experimental model systems. (2023). https://pubmed.ncbi.nlm.nih.gov/37114361/ DOI: 10.1039/d3fo00572k

route

In vitro and oral mouse exposure

tissue

NRF2-linked gene and glutathione responses

Moringa oleifera: mechanism of action and interactions (2026-09-20) · lines 68–77

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Human BEAS-2B cells and orally dosed mice · source_derived_draft · unverified_draft

## moringa-standardized-preparation-nrf2 The standardized multi-constituent ME-D leaf preparation increased NRF2-regulated NQO1 and HMOX1 expression and cellular glutathione in BEAS-2B cells, and increased NRF2-regulated genes after oral dosing in mice. Model/species: Human BEAS-2B cells and orally dosed mice Tissue/system: NRF2-linked gene and glutathione responses Exposure: Chemically profiled ME-D hot-soup or freeze-dried preparation Route: In vitro and oral mouse exposure Duration: Acute cell exposure and study-specified mouse dosing Limits: The preparation contained moringin, glucomoringin and polyphenols, so the response cannot be assigned to one constituent or treated as a human clinical outcome. Primary reference: Development of Moringa oleifera as functional food targeting NRF2 signaling: antioxidant and anti-inflammatory activity in experimental model systems. (2023). https://pubmed.ncbi.nlm.nih.gov/37114361/ DOI: 10.1039/d3fo00572k Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_access

Primary abstract

experimental_model

Conditional mouse liver knockout; kidney, adipose and pancreatic measurements.

limitations

This tissue-restricted deletion differs from complete pathway loss and from human deficiency.

nutrient_topic

Taurine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Taurine

plain_language

Other tissues compensated when liver synthesis was impaired.

primary_references

Extrahepatic tissues compensate for loss of hepatic taurine synthesis in mice with liver-specific knockout of cysteine dioxygenase. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22414809/ · DOI 10.1152/ajpendo.00589.2011

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 97–103

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Conditional mouse liver knockout; kidney, adipose and pancreatic measurements. · source_derived_draft · unverified_draft

## taurine-hepatic-compensation Other tissues compensated when liver synthesis was impaired. Liver-specific Cdo1 deletion increased extrahepatic CDO abundance and hypotaurine; mice maintained taurine, glutathione and sulfate despite a taurine-free diet. Model: Conditional mouse liver knockout; kidney, adipose and pancreatic measurements. Limitations: This tissue-restricted deletion differs from complete pathway loss and from human deficiency. Evidence access: Primary abstract Extrahepatic tissues compensate for loss of hepatic taurine synthesis in mice with liver-specific knockout of cysteine dioxygenase. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22414809/ · DOI 10.1152/ajpendo.00589.2011

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human HepG2 loss/gain-of-function experiments.

limitations

Not a selective rescue test proving all luteolin effects require SLC7A11.

nutrient_topic

Luteolin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Luteolin / 3′,4′,5,7-tetrahydroxyflavone

plain_language

Precursor handling and peroxide defense are linked.

primary_references

Luteolin attenuates CCl4-induced hepatic injury by inhibiting ferroptosis via SLC7A11. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38755566/ · DOI 10.1186/s12906-024-04486-2

trigger_kind

machinery_impairment Imported condition classification; unverified.

Luteolin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 524–530

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human HepG2 loss/gain-of-function experiments. · source_derived_draft · unverified_draft

## luteolin-slc7a11-knockdown Precursor handling and peroxide defense are linked. SLC7A11 silencing lowered GPX4/FTMT expression and total glutathione while worsening ferroptosis-associated measurements in HepG2 cells. Model: Human HepG2 loss/gain-of-function experiments. Limitations: Not a selective rescue test proving all luteolin effects require SLC7A11. Evidence access: Primary full text Luteolin attenuates CCl4-induced hepatic injury by inhibiting ferroptosis via SLC7A11. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38755566/ · DOI 10.1186/s12906-024-04486-2

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Pharmacological inhibition in human cancer-cell experiments; dose/duration not in accessed abstract.

limitations

Experimental synthesis inhibition is not a dietary cucurbitacin deficiency or evidence that oral glutathione protects people.

nutrient_topic

Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins

plain_language

Weakening glutathione production increased sensitivity in this model.

primary_references

Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008

trigger_kind

machinery_impairment Imported condition classification; unverified.

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 140–146

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Pharmacological inhibition in human cancer-cell experiments; dose/duration not in accessed abstract. · source_derived_draft · unverified_draft

## cucurbitacin-b-bso-sensitivity Weakening glutathione production increased sensitivity in this model. Pretreating human NSCLC cells with the glutathione-synthesis inhibitor BSO increased cucurbitacin B cytotoxicity. Model: Pharmacological inhibition in human cancer-cell experiments; dose/duration not in accessed abstract. Limitations: Experimental synthesis inhibition is not a dietary cucurbitacin deficiency or evidence that oral glutathione protects people. Evidence access: Primary abstract Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008

evidence_access

Primary abstract

experimental_model

Human nasopharyngeal-cancer cells; animal tumor work also reported.

limitations

Expression is not direct GPX4 binding or evidence of selenium depletion.

nutrient_topic

Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins

plain_language

A lipid-peroxide defense protein decreased in this model.

primary_references

Induction of ferroptosis in human nasopharyngeal cancer cells by cucurbitacin B: molecular mechanism and therapeutic potential. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33664249/ · DOI 10.1038/s41419-021-03516-y

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 244–250

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human nasopharyngeal-cancer cells; animal tumor work also reported. · source_derived_draft · unverified_draft

## cucurbitacin-b-gpx4-expression A lipid-peroxide defense protein decreased in this model. Cucurbitacin B exposure decreased GPX4 protein expression in the human nasopharyngeal-cancer experiments. Model: Human nasopharyngeal-cancer cells; animal tumor work also reported. Limitations: Expression is not direct GPX4 binding or evidence of selenium depletion. Evidence access: Primary abstract Induction of ferroptosis in human nasopharyngeal cancer cells by cucurbitacin B: molecular mechanism and therapeutic potential. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33664249/ · DOI 10.1038/s41419-021-03516-y

evidence_access

Primary abstract

experimental_model

Human NSCLC experiments; concentration and duration unavailable in accessed abstract.

limitations

Associated readouts do not by themselves order iron release, glutathione loss and lipid oxidation.

nutrient_topic

Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins

plain_language

Iron and antioxidant balance changed together with membrane damage.

primary_references

Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38950838/ · DOI 10.1016/j.ejphar.2024.176805

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 260–266

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human NSCLC experiments; concentration and duration unavailable in accessed abstract. · source_derived_draft · unverified_draft

## cucurbitacin-b-lipid-iron Iron and antioxidant balance changed together with membrane damage. Cucurbitacin B increased lipid ROS, malondialdehyde and measured ferrous iron while lowering glutathione in H358 and A549 experiments. Model: Human NSCLC experiments; concentration and duration unavailable in accessed abstract. Limitations: Associated readouts do not by themselves order iron release, glutathione loss and lipid oxidation. Evidence access: Primary abstract Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38950838/ · DOI 10.1016/j.ejphar.2024.176805

evidence_access

Primary abstract

experimental_model

Human NSCLC experiments plus separate cell-free interaction assays.

limitations

Compound trapping and redox effects are not distinguished by rescue alone.

nutrient_topic

Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins

plain_language

Thiol availability changed the experimental response.

primary_references

Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 148–154

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human NSCLC experiments plus separate cell-free interaction assays. · source_derived_draft · unverified_draft

## cucurbitacin-b-nac-rescue Thiol availability changed the experimental response. Adding N-acetylcysteine attenuated the reported cucurbitacin B cellular effects in the human NSCLC study. Model: Human NSCLC experiments plus separate cell-free interaction assays. Limitations: Compound trapping and redox effects are not distinguished by rescue alone. Evidence access: Primary abstract Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008

evidence_access

Primary abstract

experimental_model

Rat LC-MS study; also hydrolysis, reduction, epoxidation, amination and other conjugation routes reported.

limitations

No human mass balance or obligatory single detoxification pathway was established.

nutrient_topic

Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins

plain_language

The existing glutathione node connects chemical interception to metabolism.

primary_references

Metabolic fate of the natural anticancer agent cucurbitacin B: an LC-MS/MS-enabled profiling of its major phase I and II conjugates in vivo. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39441433/ · DOI 10.1007/s00216-024-05608-y

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 372–378

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat LC-MS study; also hydrolysis, reduction, epoxidation, amination and other conjugation routes reported. · source_derived_draft · unverified_draft

## cucurbitacin-b-rat-gsh-metabolism The existing glutathione node connects chemical interception to metabolism. Rat cucurbitacin B metabolism profiling identified glutathione conjugation among the phase-II routes. Model: Rat LC-MS study; also hydrolysis, reduction, epoxidation, amination and other conjugation routes reported. Limitations: No human mass balance or obligatory single detoxification pathway was established. Evidence access: Primary abstract Metabolic fate of the natural anticancer agent cucurbitacin B: an LC-MS/MS-enabled profiling of its major phase I and II conjugates in vivo. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39441433/ · DOI 10.1007/s00216-024-05608-y

evidence_access

Primary abstract

experimental_model

Human NSCLC cell study.

limitations

A ratio alone does not establish which synthesis, oxidation, conjugation or export flux caused the change.

nutrient_topic

Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins

plain_language

The redox balance shifted alongside toxicity.

primary_references

Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 132–138

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human NSCLC cell study. · source_derived_draft · unverified_draft

## cucurbitacin-b-redox-ratio The redox balance shifted alongside toxicity. Cucurbitacin B exposure lowered the GSH/GSSG ratio in the human NSCLC experiments. Model: Human NSCLC cell study. Limitations: A ratio alone does not establish which synthesis, oxidation, conjugation or export flux caused the change. Evidence access: Primary abstract Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008

dose

Eugenol with peroxidase/hydrogen peroxide plus ascorbate or glutathione

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Cell-free peroxidase systems and human HL-60 cells

limitations

Cell-free protection does not prove that vitamin supplementation prevents toxicity in exposed humans.

nutrient_topic

Eugenol chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Eugenol

organism

Cell-free peroxidase systems and human HL-60 cells

plain_language

Ascorbic acid and glutathione reduced DNA-adduct formation during in-vitro peroxidase activation of eugenol by about 66% and 90%, respectively.

primary_references

Oxidation of eugenol to form DNA adducts and 8-hydroxy-2'-deoxyguanosine: role of quinone methide derivative in DNA adduct formation. (1998). https://pubmed.ncbi.nlm.nih.gov/9525278/ DOI: 10.1093/carcin/19.3.437

route

In vitro

tissue

DNA adducts and oxidative base damage

Eugenol: mechanism of action and interactions (2026-09-20) · lines 121–130

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Cell-free peroxidase systems and human HL-60 cells · source_derived_draft · unverified_draft

## eugenol-ascorbate-gsh-adduct-protection Ascorbic acid and glutathione reduced DNA-adduct formation during in-vitro peroxidase activation of eugenol by about 66% and 90%, respectively. Model/species: Cell-free peroxidase systems and human HL-60 cells Tissue/system: DNA adducts and oxidative base damage Exposure: Eugenol with peroxidase/hydrogen peroxide plus ascorbate or glutathione Route: In vitro Duration: Acute Limits: Cell-free protection does not prove that vitamin supplementation prevents toxicity in exposed humans. Primary reference: Oxidation of eugenol to form DNA adducts and 8-hydroxy-2'-deoxyguanosine: role of quinone methide derivative in DNA adduct formation. (1998). https://pubmed.ncbi.nlm.nih.gov/9525278/ DOI: 10.1093/carcin/19.3.437 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Eugenol 100 micromolar

duration

30 minutes

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Phorbol-ester-stimulated human polymorphonuclear leukocytes

limitations

The large loss required activated cells and a high direct exposure; it is not evidence that culinary cloves cause systemic glutathione deficiency.

nutrient_topic

Eugenol chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Eugenol

organism

Phorbol-ester-stimulated human polymorphonuclear leukocytes

plain_language

Activated human polymorphonuclear leukocytes exposed to 100 micromolar eugenol lost about 90% of intracellular glutathione over 30 minutes.

primary_references

Metabolic activation of eugenol by myeloperoxidase and polymorphonuclear leukocytes. (1989). https://pubmed.ncbi.nlm.nih.gov/2562421/ DOI: 10.1021/tx00009a011

route

In vitro

tissue

Intracellular glutathione and oxidative burst

Eugenol: mechanism of action and interactions (2026-09-20) · lines 99–108

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Phorbol-ester-stimulated human polymorphonuclear leukocytes · source_derived_draft · unverified_draft

## eugenol-gsh-depletion Activated human polymorphonuclear leukocytes exposed to 100 micromolar eugenol lost about 90% of intracellular glutathione over 30 minutes. Model/species: Phorbol-ester-stimulated human polymorphonuclear leukocytes Tissue/system: Intracellular glutathione and oxidative burst Exposure: Eugenol 100 micromolar Route: In vitro Duration: 30 minutes Limits: The large loss required activated cells and a high direct exposure; it is not evidence that culinary cloves cause systemic glutathione deficiency. Primary reference: Metabolic activation of eugenol by myeloperoxidase and polymorphonuclear leukocytes. (1989). https://pubmed.ncbi.nlm.nih.gov/2562421/ DOI: 10.1021/tx00009a011 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

availability_state

machinery_impairment Imported condition classification; unverified.

dose

Eugenol or quinone methide with glutathione ethyl ester

duration

Minutes to cell-death assessment

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Cultured rat liver Clone 9 cells

limitations

A cell-permeable experimental glutathione ester is not equivalent to dietary glutathione supplementation.

nutrient_topic

Eugenol chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Eugenol

organism

Cultured rat liver Clone 9 cells

plain_language

Glutathione ethyl ester raised intracellular glutathione and completely protected cultured rat liver cells from eugenol- or quinone-methide-induced death.

primary_references

Comparative toxicity of eugenol and its quinone methide metabolite in cultured liver cells using kinetic fluorescence bioassays. (1998). https://pubmed.ncbi.nlm.nih.gov/9512727/ DOI: 10.1006/taap.1997.8348

route

In vitro

tissue

Glutathione, membrane physiology and cell death

trigger_kind

machinery_impairment Imported condition classification; unverified.

Eugenol: mechanism of action and interactions (2026-09-20) · lines 110–119

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Cultured rat liver Clone 9 cells · source_derived_draft · unverified_draft

## eugenol-gsh-rescue Glutathione ethyl ester raised intracellular glutathione and completely protected cultured rat liver cells from eugenol- or quinone-methide-induced death. Model/species: Cultured rat liver Clone 9 cells Tissue/system: Glutathione, membrane physiology and cell death Exposure: Eugenol or quinone methide with glutathione ethyl ester Route: In vitro Duration: Minutes to cell-death assessment Limits: A cell-permeable experimental glutathione ester is not equivalent to dietary glutathione supplementation. Primary reference: Comparative toxicity of eugenol and its quinone methide metabolite in cultured liver cells using kinetic fluorescence bioassays. (1998). https://pubmed.ncbi.nlm.nih.gov/9512727/ DOI: 10.1006/taap.1997.8348 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human erythrocytes; DIDS pharmacological intervention.

limitations

DIDS is an inhibitor, not itself an exchanger; pharmacology does not establish a unique SLC4A1 transport substrate or route.

nutrient_topic

Vanadium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Vanadium

plain_language

Membrane transport can gate the redox response.

primary_references

Efflux of glutathione and glutathione complexes from human erythrocytes in response to vanadate. · 2013 · https://pubmed.ncbi.nlm.nih.gov/22824382/ · DOI 10.1016/j.bcmd.2012.07.001

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 166–172

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human erythrocytes; DIDS pharmacological intervention. · source_derived_draft · unverified_draft

## vanadium-anion-exchanger-block Membrane transport can gate the redox response. DIDS inhibited the intracellular thiol decrease and extracellular increase during vanadate exposure, supporting an anion-transport-dependent step. Model: Human erythrocytes; DIDS pharmacological intervention. Limitations: DIDS is an inhibitor, not itself an exchanger; pharmacology does not establish a unique SLC4A1 transport substrate or route. Evidence access: Primary abstract Efflux of glutathione and glutathione complexes from human erythrocytes in response to vanadate. · 2013 · https://pubmed.ncbi.nlm.nih.gov/22824382/ · DOI 10.1016/j.bcmd.2012.07.001

evidence_access

Primary abstract

experimental_model

Isolated human erythrocytes; millimolar vanadate exposures up to four hours.

limitations

High ex-vivo concentrations; nonprotein sulfhydryl assays are not exclusively glutathione measurements.

nutrient_topic

Vanadium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Vanadium

plain_language

Loss of an intracellular thiol pool can include export rather than only oxidation.

primary_references

Efflux of glutathione and glutathione complexes from human erythrocytes in response to vanadate. · 2013 · https://pubmed.ncbi.nlm.nih.gov/22824382/ · DOI 10.1016/j.bcmd.2012.07.001

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 158–164

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated human erythrocytes; millimolar vanadate exposures up to four hours. · source_derived_draft · unverified_draft

## vanadium-erythrocyte-gsh Loss of an intracellular thiol pool can include export rather than only oxidation. Vanadate exposure depleted intracellular nonprotein sulfhydryls while increasing extracellular glutathione in human erythrocytes. Model: Isolated human erythrocytes; millimolar vanadate exposures up to four hours. Limitations: High ex-vivo concentrations; nonprotein sulfhydryl assays are not exclusively glutathione measurements. Evidence access: Primary abstract Efflux of glutathione and glutathione complexes from human erythrocytes in response to vanadate. · 2013 · https://pubmed.ncbi.nlm.nih.gov/22824382/ · DOI 10.1016/j.bcmd.2012.07.001

evidence_access

Primary abstract

experimental_model

Ex-vivo supernatant treatment.

limitations

This supports but does not structurally identify every GSH–vanadium complex; not clinical chelation guidance.

nutrient_topic

Vanadium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Vanadium

plain_language

An assay can detect additional glutathione after a complex is disrupted.

primary_references

Efflux of glutathione and glutathione complexes from human erythrocytes in response to vanadate. · 2013 · https://pubmed.ncbi.nlm.nih.gov/22824382/ · DOI 10.1016/j.bcmd.2012.07.001

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 182–188

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Ex-vivo supernatant treatment. · source_derived_draft · unverified_draft

## vanadium-gsh-complex-recovery An assay can detect additional glutathione after a complex is disrupted. DMSA treatment of erythrocyte supernatants increased measured glutathione, consistent with release from metal-associated forms. Model: Ex-vivo supernatant treatment. Limitations: This supports but does not structurally identify every GSH–vanadium complex; not clinical chelation guidance. Evidence access: Primary abstract Efflux of glutathione and glutathione complexes from human erythrocytes in response to vanadate. · 2013 · https://pubmed.ncbi.nlm.nih.gov/22824382/ · DOI 10.1016/j.bcmd.2012.07.001

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human erythrocyte inhibitor experiment.

limitations

The accessed study does not identify a specific ABCC isoform; no invented transporter assignment.

nutrient_topic

Vanadium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Vanadium

plain_language

An exporter can contribute to loss of cellular glutathione.

primary_references

Efflux of glutathione and glutathione complexes from human erythrocytes in response to vanadate. · 2013 · https://pubmed.ncbi.nlm.nih.gov/22824382/ · DOI 10.1016/j.bcmd.2012.07.001

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 174–180

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human erythrocyte inhibitor experiment. · source_derived_draft · unverified_draft

## vanadium-mrp-efflux-block An exporter can contribute to loss of cellular glutathione. MK571 reduced glutathione efflux during erythrocyte vanadate exposure, suggesting involvement of an MRP-family exporter. Model: Human erythrocyte inhibitor experiment. Limitations: The accessed study does not identify a specific ABCC isoform; no invented transporter assignment. Evidence access: Primary abstract Efflux of glutathione and glutathione complexes from human erythrocytes in response to vanadate. · 2013 · https://pubmed.ncbi.nlm.nih.gov/22824382/ · DOI 10.1016/j.bcmd.2012.07.001

evidence_span

{"source_cache": "artifacts/ceylon-research/32788161.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "431169f83241cb83b84dd81d84eb1db225735677cabf33f09af8b1e22dfe64f4", "start_char": 0, "end_char": 2507, "text_sha256": "431169f83241cb83b84dd81d84eb1db225735677cabf33f09af8b1e22dfe64f4"}

experimental_model

CYP2A6 mass spectrometry, time-dependent inhibition and numerical modeling

exposure

Cinnamaldehyde and separately 2-methoxycinnamaldehyde; model exposure approximately 275 mg cinnamaldehyde

limitations

Rat-scaled predicted human AUC is not observed AUC. Heme loss was specifically reported for the methoxy analogue; apoprotein adduction is a different endpoint from inhibition.

nutrient_topic

Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. · Ceylon cinnamon / Cinnamomum verum bark preparations

organism

Human CYP2A6; rat-scaled modeling parameters

plain_language

The protein acquired extra mass even with glutathione present. This differs from measuring how much enzyme activity survives.

primary_references

[ceylon-p32788161] Mechanisms of Herb-Drug Interactions Involving Cinnamon and CYP2A6: Focus on Time-Dependent Inhibition by Cinnamaldehyde and 2-Methoxycinnamaldehyde. (2020). https://pubmed.ncbi.nlm.nih.gov/32788161/ DOI: 10.1124/dmd.120.000087

tissue_or_cell_type

Enzyme apoprotein/heme; simulated drug exposure

Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17) · lines 766–777

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CYP2A6 mass spectrometry, time-dependent inhibition and numerical modeling · source_derived_draft · unverified_draft

### ceylon-cyp-adduct Mass spectra indicated cinnamaldehyde-associated CYP2A6 apoprotein adduction, with reported mass addition about 132.67 Da; added glutathione did not prevent this measured adduction. Condition category: normal nutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. plain_language: The protein acquired extra mass even with glutathione present. This differs from measuring how much enzyme activity survives. organism: Human CYP2A6; rat-scaled modeling parameters tissue_or_cell_type: Enzyme apoprotein/heme; simulated drug exposure experimental_model: CYP2A6 mass spectrometry, time-dependent inhibition and numerical modeling limitations: Rat-scaled predicted human AUC is not observed AUC. Heme loss was specifically reported for the methoxy analogue; apoprotein adduction is a different endpoint from inhibition. exposure: Cinnamaldehyde and separately 2-methoxycinnamaldehyde; model exposure approximately 275 mg cinnamaldehyde evidence_span: {"source_cache": "artifacts/ceylon-research/32788161.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "431169f83241cb83b84dd81d84eb1db225735677cabf33f09af8b1e22dfe64f4", "start_char": 0, "end_char": 2507, "text_sha256": "431169f83241cb83b84dd81d84eb1db225735677cabf33f09af8b1e22dfe64f4"} [ceylon-p32788161] Mechanisms of Herb-Drug Interactions Involving Cinnamon and CYP2A6: Focus on Time-Dependent Inhibition by Cinnamaldehyde and 2-Methoxycinnamaldehyde. (2020). https://pubmed.ncbi.nlm.nih.gov/32788161/ DOI: 10.1124/dmd.120.000087

evidence_span

{"source_cache": "artifacts/ceylon-research/25712056.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ad37b0dca440e7fa609a46cf02377c2979d2be8e09291a370efb963ff3c9cfd", "start_char": 0, "end_char": 1920, "text_sha256": "8ad37b0dca440e7fa609a46cf02377c2979d2be8e09291a370efb963ff3c9cfd"}

experimental_model

HCT116 mechanism and AOM/DSS knockout-mouse experiment

exposure

Purified cinnamaldehyde cell exposure and dietary supplementation in mice

limitations

No human cancer-prevention outcome; the abstract identifies C151 dependence but does not resolve the transfected KEAP1 construct species.

nutrient_topic

Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. · Ceylon cinnamon / Cinnamomum verum bark preparations

organism

Human HCT116 cells; KEAP1 construct species unresolved

plain_language

These cells accumulated more glutathione; that does not measure whole-body glutathione supply.

primary_references

[ceylon-p25712056] Nrf2-dependent suppression of azoxymethane/dextran sulfate sodium-induced colon carcinogenesis by the cinnamon-derived dietary factor cinnamaldehyde. (2015). https://pubmed.ncbi.nlm.nih.gov/25712056/ DOI: 10.1158/1940-6207.capr-14-0359

tissue_or_cell_type

Colon epithelial cancer cells and experimental inflammatory colon tumors

Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17) · lines 623–634

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HCT116 mechanism and AOM/DSS knockout-mouse experiment · source_derived_draft · unverified_draft

### ceylon-nrf2-gsh Cinnamaldehyde increased cellular glutathione in the HCT116 NRF2-response study. Condition category: normal nutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. plain_language: These cells accumulated more glutathione; that does not measure whole-body glutathione supply. organism: Human HCT116 cells; KEAP1 construct species unresolved tissue_or_cell_type: Colon epithelial cancer cells and experimental inflammatory colon tumors experimental_model: HCT116 mechanism and AOM/DSS knockout-mouse experiment limitations: No human cancer-prevention outcome; the abstract identifies C151 dependence but does not resolve the transfected KEAP1 construct species. exposure: Purified cinnamaldehyde cell exposure and dietary supplementation in mice evidence_span: {"source_cache": "artifacts/ceylon-research/25712056.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ad37b0dca440e7fa609a46cf02377c2979d2be8e09291a370efb963ff3c9cfd", "start_char": 0, "end_char": 1920, "text_sha256": "8ad37b0dca440e7fa609a46cf02377c2979d2be8e09291a370efb963ff3c9cfd"} [ceylon-p25712056] Nrf2-dependent suppression of azoxymethane/dextran sulfate sodium-induced colon carcinogenesis by the cinnamon-derived dietary factor cinnamaldehyde. (2015). https://pubmed.ncbi.nlm.nih.gov/25712056/ DOI: 10.1158/1940-6207.capr-14-0359

evidence_access

Primary abstract

experimental_model

Mouse liver signaling and dietary experiments.

limitations

The proposed glutathione-sensing mechanism is not evidence of direct methionine binding to PERK.

nutrient_topic

L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine

plain_language

Dietary sulfur status engaged an alternative stress-response route.

primary_references

Role of GCN2-Independent Signaling Through a Noncanonical PERK/NRF2 Pathway in the Physiological Responses to Dietary Methionine Restriction. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26936965/ · DOI 10.2337/db15-1324

L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 388–394

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse liver signaling and dietary experiments. · source_derived_draft · unverified_draft

## methionine-perk-redox-response Dietary sulfur status engaged an alternative stress-response route. Methionine restriction activated hepatic PERK and an antioxidant/ISR program in wild-type and Gcn2-null mice, without the measured ER-stress pattern. Model: Mouse liver signaling and dietary experiments. Limitations: The proposed glutathione-sensing mechanism is not evidence of direct methionine binding to PERK. Evidence access: Primary abstract Role of GCN2-Independent Signaling Through a Noncanonical PERK/NRF2 Pathway in the Physiological Responses to Dietary Methionine Restriction. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26936965/ · DOI 10.2337/db15-1324

evidence_access

Primary abstract

experimental_model

Patient-derived colorectal xenografts and Kras/Trp53-driven mouse sarcoma; antimetabolite/radiation settings.

limitations

Different models and immune contexts from other tumor studies; not a human cancer efficacy trial.

nutrient_topic

L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine

plain_language

Diet composition modified pathways also targeted by cancer treatment.

primary_references

Dietary methionine influences therapy in mouse cancer models and alters human metabolism. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31367041/ · DOI 10.1038/s41586-019-1437-3

L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 484–490

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Patient-derived colorectal xenografts and Kras/Trp53-driven mouse sarcoma; antimetabolite/radiation settings. · source_derived_draft · unverified_draft

## methionine-restriction-therapy-metabolism Diet composition modified pathways also targeted by cancer treatment. Restriction altered one-carbon, nucleotide and redox metabolism and improved treatment responses in colorectal xenograft and autochthonous sarcoma models. Model: Patient-derived colorectal xenografts and Kras/Trp53-driven mouse sarcoma; antimetabolite/radiation settings. Limitations: Different models and immune contexts from other tumor studies; not a human cancer efficacy trial. Evidence access: Primary abstract Dietary methionine influences therapy in mouse cancer models and alters human metabolism. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31367041/ · DOI 10.1038/s41586-019-1437-3

evidence_span

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experimental_model

Randomized placebo-controlled beverage trial

exposure

600 micromol glucoraphanin plus 40 micromol sulforaphane daily for 12 weeks

limitations

Urinary conjugate excretion is not proof of reduced cancer incidence, removal of every toxin or a clinical detoxification indication.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human, 291 recruited adults in Qidong

plain_language

The result extended to a second measured pollutant.

primary_references

[sulforaphane-p24913818] Rapid and sustainable detoxication of airborne pollutants by broccoli sprout beverage: results of a randomized clinical trial in China. (2014). https://pubmed.ncbi.nlm.nih.gov/24913818/ DOI: 10.1158/1940-6207.capr-14-0103

tissue_or_cell_type

Urinary pollutant mercapturates

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 1061–1072

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled beverage trial · source_derived_draft · unverified_draft

### sulforaphane-acrolein-excretion Urinary acrolein-derived conjugate excretion increased by 23%. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The result extended to a second measured pollutant. organism: Human, 291 recruited adults in Qidong tissue_or_cell_type: Urinary pollutant mercapturates experimental_model: Randomized placebo-controlled beverage trial limitations: Urinary conjugate excretion is not proof of reduced cancer incidence, removal of every toxin or a clinical detoxification indication. exposure: 600 micromol glucoraphanin plus 40 micromol sulforaphane daily for 12 weeks evidence_span: {"source_cache": "artifacts/sulforaphane-research/24913818.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dabcc8a48260f668232ae3ab528fbf08e7b8b814ad9959d709fcd4702bbda7dd", "start_char": 0, "end_char": 1710, "text_sha256": "dabcc8a48260f668232ae3ab528fbf08e7b8b814ad9959d709fcd4702bbda7dd"} [sulforaphane-p24913818] Rapid and sustainable detoxication of airborne pollutants by broccoli sprout beverage: results of a randomized clinical trial in China. (2014). https://pubmed.ncbi.nlm.nih.gov/24913818/ DOI: 10.1158/1940-6207.capr-14-0103

evidence_span

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experimental_model

Randomized placebo-controlled beverage trial

exposure

600 micromol glucoraphanin plus 40 micromol sulforaphane daily for 12 weeks

limitations

Urinary conjugate excretion is not proof of reduced cancer incidence, removal of every toxin or a clinical detoxification indication.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human, 291 recruited adults in Qidong

plain_language

A specific exposure-processing marker increased.

primary_references

[sulforaphane-p24913818] Rapid and sustainable detoxication of airborne pollutants by broccoli sprout beverage: results of a randomized clinical trial in China. (2014). https://pubmed.ncbi.nlm.nih.gov/24913818/ DOI: 10.1158/1940-6207.capr-14-0103

tissue_or_cell_type

Urinary pollutant mercapturates

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 1048–1059

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled beverage trial · source_derived_draft · unverified_draft

### sulforaphane-benzene-excretion The intervention increased urinary benzene-derived conjugate excretion by 61% compared with placebo. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: A specific exposure-processing marker increased. organism: Human, 291 recruited adults in Qidong tissue_or_cell_type: Urinary pollutant mercapturates experimental_model: Randomized placebo-controlled beverage trial limitations: Urinary conjugate excretion is not proof of reduced cancer incidence, removal of every toxin or a clinical detoxification indication. exposure: 600 micromol glucoraphanin plus 40 micromol sulforaphane daily for 12 weeks evidence_span: {"source_cache": "artifacts/sulforaphane-research/24913818.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dabcc8a48260f668232ae3ab528fbf08e7b8b814ad9959d709fcd4702bbda7dd", "start_char": 0, "end_char": 1710, "text_sha256": "dabcc8a48260f668232ae3ab528fbf08e7b8b814ad9959d709fcd4702bbda7dd"} [sulforaphane-p24913818] Rapid and sustainable detoxication of airborne pollutants by broccoli sprout beverage: results of a randomized clinical trial in China. (2014). https://pubmed.ncbi.nlm.nih.gov/24913818/ DOI: 10.1158/1940-6207.capr-14-0103

evidence_span

{"source_cache": "artifacts/sulforaphane-research/24913818.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dabcc8a48260f668232ae3ab528fbf08e7b8b814ad9959d709fcd4702bbda7dd", "start_char": 0, "end_char": 1710, "text_sha256": "dabcc8a48260f668232ae3ab528fbf08e7b8b814ad9959d709fcd4702bbda7dd"}

experimental_model

Randomized placebo-controlled beverage trial

exposure

600 micromol glucoraphanin plus 40 micromol sulforaphane daily for 12 weeks

limitations

Urinary conjugate excretion is not proof of reduced cancer incidence, removal of every toxin or a clinical detoxification indication.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human, 291 recruited adults in Qidong

plain_language

The response was selective rather than a universal detoxification boost.

primary_references

[sulforaphane-p24913818] Rapid and sustainable detoxication of airborne pollutants by broccoli sprout beverage: results of a randomized clinical trial in China. (2014). https://pubmed.ncbi.nlm.nih.gov/24913818/ DOI: 10.1158/1940-6207.capr-14-0103

tissue_or_cell_type

Urinary pollutant mercapturates

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 1074–1085

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled beverage trial · source_derived_draft · unverified_draft

### sulforaphane-crotonaldehyde-null Crotonaldehyde-derived conjugate excretion did not show the intervention increase observed for benzene and acrolein. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response was selective rather than a universal detoxification boost. organism: Human, 291 recruited adults in Qidong tissue_or_cell_type: Urinary pollutant mercapturates experimental_model: Randomized placebo-controlled beverage trial limitations: Urinary conjugate excretion is not proof of reduced cancer incidence, removal of every toxin or a clinical detoxification indication. exposure: 600 micromol glucoraphanin plus 40 micromol sulforaphane daily for 12 weeks evidence_span: {"source_cache": "artifacts/sulforaphane-research/24913818.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dabcc8a48260f668232ae3ab528fbf08e7b8b814ad9959d709fcd4702bbda7dd", "start_char": 0, "end_char": 1710, "text_sha256": "dabcc8a48260f668232ae3ab528fbf08e7b8b814ad9959d709fcd4702bbda7dd"} [sulforaphane-p24913818] Rapid and sustainable detoxication of airborne pollutants by broccoli sprout beverage: results of a randomized clinical trial in China. (2014). https://pubmed.ncbi.nlm.nih.gov/24913818/ DOI: 10.1158/1940-6207.capr-14-0103

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sulforaphane-research/12663510.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "95f1de031ede41aa12f975dff28193dcb426465d4bda94bb84d4e60ef6c292b9", "start_char": 0, "end_char": 1535, "text_sha256": "95f1de031ede41aa12f975dff28193dcb426465d4bda94bb84d4e60ef6c292b9"}

experimental_model

Transcription/translation and inhibitor experiments

exposure

Sulforaphane, sodium selenite, combined treatment and pathway inhibitors

limitations

Cell-culture synergy at specified exposures is not a clinical supplement recommendation; TXNRD1 and TXNRD2 were not interchangeable.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human HepG2 hepatoma cells

plain_language

The signaling response depended on the surrounding glutathione system.

primary_references

[sulforaphane-p12663510] Synergy between sulforaphane and selenium in the induction of thioredoxin reductase 1 requires both transcriptional and translational modulation. (2003). https://pubmed.ncbi.nlm.nih.gov/12663510/ DOI: 10.1093/carcin/24.3.497

tissue_or_cell_type

Thioredoxin reductase regulation

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 762–773

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transcription/translation and inhibitor experiments · source_derived_draft · unverified_draft

### sulforaphane-gsh-gates-induction BSO pretreatment significantly reduced sulforaphane-induced TXNRD1 mRNA. Condition category: machinery_impairment nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The signaling response depended on the surrounding glutathione system. organism: Human HepG2 hepatoma cells tissue_or_cell_type: Thioredoxin reductase regulation experimental_model: Transcription/translation and inhibitor experiments limitations: Cell-culture synergy at specified exposures is not a clinical supplement recommendation; TXNRD1 and TXNRD2 were not interchangeable. exposure: Sulforaphane, sodium selenite, combined treatment and pathway inhibitors evidence_span: {"source_cache": "artifacts/sulforaphane-research/12663510.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "95f1de031ede41aa12f975dff28193dcb426465d4bda94bb84d4e60ef6c292b9", "start_char": 0, "end_char": 1535, "text_sha256": "95f1de031ede41aa12f975dff28193dcb426465d4bda94bb84d4e60ef6c292b9"} [sulforaphane-p12663510] Synergy between sulforaphane and selenium in the induction of thioredoxin reductase 1 requires both transcriptional and translational modulation. (2003). https://pubmed.ncbi.nlm.nih.gov/12663510/ DOI: 10.1093/carcin/24.3.497

evidence_span

{"source_cache": "artifacts/sulforaphane-research/30581542.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77cf6674cf9b9bc140a228588a53c937966fd3a67397c1c4970221c5cc58a0b1", "start_char": 1428, "end_char": 1604, "text_sha256": "a5d33b10162adea5e60fcff380eabf7e272963711914ea0e8e7091ad8c79df21"}

experimental_model

Human enzyme mutagenesis, kinetics and molecular dynamics

exposure

S-loop variants; established biosynthetic reactions described in the introduction

limitations

Reaction descriptions are background chemistry in a primary enzyme paper, not evidence that sulforaphane corrects inherited GSS deficiency.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human GSS

plain_language

The induced glutathione pathway still depends on ordinary enzyme cofactors.

primary_references

[sulforaphane-p30581542] Genetic Mutations in the S-loop of Human Glutathione Synthetase: Links Between Substrate Binding, Active Site Structure and Allostery. (2019). https://pubmed.ncbi.nlm.nih.gov/30581542/ DOI: 10.1016/j.csbj.2018.11.008

tissue_or_cell_type

Glutathione synthesis and substrate binding

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 866–877

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human enzyme mutagenesis, kinetics and molecular dynamics · source_derived_draft · unverified_draft

### sulforaphane-gss-magnesium The human GSS active sites bind ATP and associated magnesium for peptide-bond formation. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The induced glutathione pathway still depends on ordinary enzyme cofactors. organism: Human GSS tissue_or_cell_type: Glutathione synthesis and substrate binding experimental_model: Human enzyme mutagenesis, kinetics and molecular dynamics limitations: Reaction descriptions are background chemistry in a primary enzyme paper, not evidence that sulforaphane corrects inherited GSS deficiency. exposure: S-loop variants; established biosynthetic reactions described in the introduction evidence_span: {"source_cache": "artifacts/sulforaphane-research/30581542.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77cf6674cf9b9bc140a228588a53c937966fd3a67397c1c4970221c5cc58a0b1", "start_char": 1428, "end_char": 1604, "text_sha256": "a5d33b10162adea5e60fcff380eabf7e272963711914ea0e8e7091ad8c79df21"} [sulforaphane-p30581542] Genetic Mutations in the S-loop of Human Glutathione Synthetase: Links Between Substrate Binding, Active Site Structure and Allostery. (2019). https://pubmed.ncbi.nlm.nih.gov/30581542/ DOI: 10.1016/j.csbj.2018.11.008

evidence_span

{"source_cache": "artifacts/sulforaphane-research/7826396.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe", "start_char": 0, "end_char": 989, "text_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe"}

experimental_model

Recombinant human GST conjugation and reverse-reaction kinetics

exposure

Four isothiocyanates and GSTP1-1, GSTM1-1, GSTA1-1 and GSTM2-2

limitations

Relative enzyme rates are not whole-person clearance predictions; reverse reactions were slower and inhibited by high GSH.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human GST isoenzymes

plain_language

Different GST isoenzymes can participate in this route.

primary_references

[sulforaphane-p7826396] Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases. (1995). https://pubmed.ncbi.nlm.nih.gov/7826396/ DOI: 10.1006/bbrc.1995.1106

tissue_or_cell_type

Isothiocyanate-glutathione chemistry

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 268–279

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human GST conjugation and reverse-reaction kinetics · source_derived_draft · unverified_draft

### sulforaphane-gstm-conjugation GSTM1-1 was among the efficient tested human GST catalysts for isothiocyanate conjugation. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different GST isoenzymes can participate in this route. organism: Human GST isoenzymes tissue_or_cell_type: Isothiocyanate-glutathione chemistry experimental_model: Recombinant human GST conjugation and reverse-reaction kinetics limitations: Relative enzyme rates are not whole-person clearance predictions; reverse reactions were slower and inhibited by high GSH. exposure: Four isothiocyanates and GSTP1-1, GSTM1-1, GSTA1-1 and GSTM2-2 evidence_span: {"source_cache": "artifacts/sulforaphane-research/7826396.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe", "start_char": 0, "end_char": 989, "text_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe"} [sulforaphane-p7826396] Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases. (1995). https://pubmed.ncbi.nlm.nih.gov/7826396/ DOI: 10.1006/bbrc.1995.1106

evidence_span

{"source_cache": "artifacts/sulforaphane-research/7826396.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe", "start_char": 0, "end_char": 989, "text_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe"}

experimental_model

Recombinant human GST conjugation and reverse-reaction kinetics

exposure

Four isothiocyanates and GSTP1-1, GSTM1-1, GSTA1-1 and GSTM2-2

limitations

Relative enzyme rates are not whole-person clearance predictions; reverse reactions were slower and inhibited by high GSH.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human GST isoenzymes

plain_language

Glutathione attaches to sulforaphane during its handling.

primary_references

[sulforaphane-p7826396] Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases. (1995). https://pubmed.ncbi.nlm.nih.gov/7826396/ DOI: 10.1006/bbrc.1995.1106

tissue_or_cell_type

Isothiocyanate-glutathione chemistry

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 255–266

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human GST conjugation and reverse-reaction kinetics · source_derived_draft · unverified_draft

### sulforaphane-gstp-conjugation GSTP1-1 catalyzed sulforaphane conjugation with glutathione in the human enzyme comparison. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione attaches to sulforaphane during its handling. organism: Human GST isoenzymes tissue_or_cell_type: Isothiocyanate-glutathione chemistry experimental_model: Recombinant human GST conjugation and reverse-reaction kinetics limitations: Relative enzyme rates are not whole-person clearance predictions; reverse reactions were slower and inhibited by high GSH. exposure: Four isothiocyanates and GSTP1-1, GSTM1-1, GSTA1-1 and GSTM2-2 evidence_span: {"source_cache": "artifacts/sulforaphane-research/7826396.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe", "start_char": 0, "end_char": 989, "text_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe"} [sulforaphane-p7826396] Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases. (1995). https://pubmed.ncbi.nlm.nih.gov/7826396/ DOI: 10.1006/bbrc.1995.1106

evidence_span

{"source_cache": "artifacts/sulforaphane-research/18204073.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0fcd98974f9fe12b2ca7c4326f94eddf4f20de4ac2ae6fdebb64de0efb1d8be9", "start_char": 0, "end_char": 1894, "text_sha256": "0fcd98974f9fe12b2ca7c4326f94eddf4f20de4ac2ae6fdebb64de0efb1d8be9"}

experimental_model

Transgenic transporter/enzyme comparison

exposure

Sulforaphane; GSH depletion control

limitations

Engineered cancer cells; enzyme expression and efflux can have opposing effects without being a scientific contradiction.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human MCF7 cells with GSTP1 and/or MRP1

plain_language

Conjugation can initially retain the exposure inside cells.

primary_references

[sulforaphane-p18204073] Expression of MRP1 and GSTP1-1 modulate the acute cellular response to treatment with the chemopreventive isothiocyanate, sulforaphane. (2008). https://pubmed.ncbi.nlm.nih.gov/18204073/ DOI: 10.1093/carcin/bgn013

tissue_or_cell_type

Intracellular retention, ARE induction and Nrf2 persistence

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 1009–1020

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transgenic transporter/enzyme comparison · source_derived_draft · unverified_draft

### sulforaphane-gstp-retention GSTP1-1 expression alone accelerated sulforaphane/conjugate accumulation and increased ARE reporter induction. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: Conjugation can initially retain the exposure inside cells. organism: Human MCF7 cells with GSTP1 and/or MRP1 tissue_or_cell_type: Intracellular retention, ARE induction and Nrf2 persistence experimental_model: Transgenic transporter/enzyme comparison limitations: Engineered cancer cells; enzyme expression and efflux can have opposing effects without being a scientific contradiction. exposure: Sulforaphane; GSH depletion control evidence_span: {"source_cache": "artifacts/sulforaphane-research/18204073.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0fcd98974f9fe12b2ca7c4326f94eddf4f20de4ac2ae6fdebb64de0efb1d8be9", "start_char": 0, "end_char": 1894, "text_sha256": "0fcd98974f9fe12b2ca7c4326f94eddf4f20de4ac2ae6fdebb64de0efb1d8be9"} [sulforaphane-p18204073] Expression of MRP1 and GSTP1-1 modulate the acute cellular response to treatment with the chemopreventive isothiocyanate, sulforaphane. (2008). https://pubmed.ncbi.nlm.nih.gov/18204073/ DOI: 10.1093/carcin/bgn013

evidence_span

{"source_cache": "artifacts/sulforaphane-research/18204073.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0fcd98974f9fe12b2ca7c4326f94eddf4f20de4ac2ae6fdebb64de0efb1d8be9", "start_char": 0, "end_char": 1894, "text_sha256": "0fcd98974f9fe12b2ca7c4326f94eddf4f20de4ac2ae6fdebb64de0efb1d8be9"}

experimental_model

Transgenic transporter/enzyme comparison

exposure

Sulforaphane; GSH depletion control

limitations

Engineered cancer cells; enzyme expression and efflux can have opposing effects without being a scientific contradiction.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human MCF7 cells with GSTP1 and/or MRP1

plain_language

The duration of the response depends partly on how the compound is handled.

primary_references

[sulforaphane-p18204073] Expression of MRP1 and GSTP1-1 modulate the acute cellular response to treatment with the chemopreventive isothiocyanate, sulforaphane. (2008). https://pubmed.ncbi.nlm.nih.gov/18204073/ DOI: 10.1093/carcin/bgn013

tissue_or_cell_type

Intracellular retention, ARE induction and Nrf2 persistence

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 1035–1046

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transgenic transporter/enzyme comparison · source_derived_draft · unverified_draft

### sulforaphane-mrp-nrf2-duration The sulforaphane-induced Nrf2 increase was less sustained in MRP1-expressing cells, especially with GSTP1 coexpression. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The duration of the response depends partly on how the compound is handled. organism: Human MCF7 cells with GSTP1 and/or MRP1 tissue_or_cell_type: Intracellular retention, ARE induction and Nrf2 persistence experimental_model: Transgenic transporter/enzyme comparison limitations: Engineered cancer cells; enzyme expression and efflux can have opposing effects without being a scientific contradiction. exposure: Sulforaphane; GSH depletion control evidence_span: {"source_cache": "artifacts/sulforaphane-research/18204073.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0fcd98974f9fe12b2ca7c4326f94eddf4f20de4ac2ae6fdebb64de0efb1d8be9", "start_char": 0, "end_char": 1894, "text_sha256": "0fcd98974f9fe12b2ca7c4326f94eddf4f20de4ac2ae6fdebb64de0efb1d8be9"} [sulforaphane-p18204073] Expression of MRP1 and GSTP1-1 modulate the acute cellular response to treatment with the chemopreventive isothiocyanate, sulforaphane. (2008). https://pubmed.ncbi.nlm.nih.gov/18204073/ DOI: 10.1093/carcin/bgn013

evidence_span

{"source_cache": "artifacts/sulforaphane-research/18204073.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0fcd98974f9fe12b2ca7c4326f94eddf4f20de4ac2ae6fdebb64de0efb1d8be9", "start_char": 0, "end_char": 1894, "text_sha256": "0fcd98974f9fe12b2ca7c4326f94eddf4f20de4ac2ae6fdebb64de0efb1d8be9"}

experimental_model

Transgenic transporter/enzyme comparison

exposure

Sulforaphane; GSH depletion control

limitations

Engineered cancer cells; enzyme expression and efflux can have opposing effects without being a scientific contradiction.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human MCF7 cells with GSTP1 and/or MRP1

plain_language

Export can counter the retention effect.

primary_references

[sulforaphane-p18204073] Expression of MRP1 and GSTP1-1 modulate the acute cellular response to treatment with the chemopreventive isothiocyanate, sulforaphane. (2008). https://pubmed.ncbi.nlm.nih.gov/18204073/ DOI: 10.1093/carcin/bgn013

tissue_or_cell_type

Intracellular retention, ARE induction and Nrf2 persistence

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 1022–1033

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transgenic transporter/enzyme comparison · source_derived_draft · unverified_draft

### sulforaphane-mrp-retention MRP1 expression reduced intracellular sulforaphane/conjugate accumulation and attenuated ARE-dependent responses. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: Export can counter the retention effect. organism: Human MCF7 cells with GSTP1 and/or MRP1 tissue_or_cell_type: Intracellular retention, ARE induction and Nrf2 persistence experimental_model: Transgenic transporter/enzyme comparison limitations: Engineered cancer cells; enzyme expression and efflux can have opposing effects without being a scientific contradiction. exposure: Sulforaphane; GSH depletion control evidence_span: {"source_cache": "artifacts/sulforaphane-research/18204073.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0fcd98974f9fe12b2ca7c4326f94eddf4f20de4ac2ae6fdebb64de0efb1d8be9", "start_char": 0, "end_char": 1894, "text_sha256": "0fcd98974f9fe12b2ca7c4326f94eddf4f20de4ac2ae6fdebb64de0efb1d8be9"} [sulforaphane-p18204073] Expression of MRP1 and GSTP1-1 modulate the acute cellular response to treatment with the chemopreventive isothiocyanate, sulforaphane. (2008). https://pubmed.ncbi.nlm.nih.gov/18204073/ DOI: 10.1093/carcin/bgn013

evidence_span

{"source_cache": "artifacts/sulforaphane-research/7826396.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe", "start_char": 0, "end_char": 989, "text_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe"}

experimental_model

Recombinant human GST conjugation and reverse-reaction kinetics

exposure

Four isothiocyanates and GSTP1-1, GSTM1-1, GSTA1-1 and GSTM2-2

limitations

Relative enzyme rates are not whole-person clearance predictions; reverse reactions were slower and inhibited by high GSH.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human GST isoenzymes

plain_language

Conjugation is reversible, so bound and free exposure are related but different.

primary_references

[sulforaphane-p7826396] Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases. (1995). https://pubmed.ncbi.nlm.nih.gov/7826396/ DOI: 10.1006/bbrc.1995.1106

tissue_or_cell_type

Isothiocyanate-glutathione chemistry

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 294–305

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human GST conjugation and reverse-reaction kinetics · source_derived_draft · unverified_draft

### sulforaphane-reverse-conjugation GSTs also catalyzed reverse cleavage of isothiocyanate-GSH conjugates; those reactions were slow and inhibited by high GSH. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: Conjugation is reversible, so bound and free exposure are related but different. organism: Human GST isoenzymes tissue_or_cell_type: Isothiocyanate-glutathione chemistry experimental_model: Recombinant human GST conjugation and reverse-reaction kinetics limitations: Relative enzyme rates are not whole-person clearance predictions; reverse reactions were slower and inhibited by high GSH. exposure: Four isothiocyanates and GSTP1-1, GSTM1-1, GSTA1-1 and GSTM2-2 evidence_span: {"source_cache": "artifacts/sulforaphane-research/7826396.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe", "start_char": 0, "end_char": 989, "text_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe"} [sulforaphane-p7826396] Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases. (1995). https://pubmed.ncbi.nlm.nih.gov/7826396/ DOI: 10.1006/bbrc.1995.1106

evidence_span

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experimental_model

Rat pretreatment and isolated mitochondrial calcium challenge

exposure

40 mg/kg mangiferin pretreatment; isolated mitochondria exposed to calcium

limitations

Mitochondrial challenge does not establish harm from usual oral intake; proposed quinone-thiol adduct mechanism was not fully proven.

nutrient_topic

Mangiferin research collection; topical membership is not evidence of a direct dietary effect. · Mangiferin

organism

Rattus norvegicus

plain_language

The calcium challenge changed the redox consequences.

primary_references

[mangiferin-p15979560] Mangiferin, a natural occurring glucosyl xanthone, increases susceptibility of rat liver mitochondria to calcium-induced permeability transition. (2005). https://pubmed.ncbi.nlm.nih.gov/15979560/ DOI: 10.1016/j.abb.2005.05.015

tissue_or_cell_type

Liver mitochondria

Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 718–729

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat pretreatment and isolated mitochondrial calcium challenge · source_derived_draft · unverified_draft

### mangiferin-calcium-gsh Calcium-challenged mitochondria from treated rats showed glutathione depletion. Condition category: normal nutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The calcium challenge changed the redox consequences. organism: Rattus norvegicus tissue_or_cell_type: Liver mitochondria experimental_model: Rat pretreatment and isolated mitochondrial calcium challenge limitations: Mitochondrial challenge does not establish harm from usual oral intake; proposed quinone-thiol adduct mechanism was not fully proven. exposure: 40 mg/kg mangiferin pretreatment; isolated mitochondria exposed to calcium evidence_span: {"source_cache": "artifacts/mangiferin-research/15979560.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3de89f65f9561fd94c5f07121e8150f116c59277658d7e611a399dc2d963ec1f", "start_char": 0, "end_char": 2234, "text_sha256": "3de89f65f9561fd94c5f07121e8150f116c59277658d7e611a399dc2d963ec1f"} [mangiferin-p15979560] Mangiferin, a natural occurring glucosyl xanthone, increases susceptibility of rat liver mitochondria to calcium-induced permeability transition. (2005). https://pubmed.ncbi.nlm.nih.gov/15979560/ DOI: 10.1016/j.abb.2005.05.015

evidence_span

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experimental_model

Iron-coordination spectroscopy and mitochondrial challenge

exposure

Assay-defined ferric iron-mangiferin complex

limitations

Defined chemical form and calcium context explain the different response; no clinical iron/mangiferin co-dosing recommendation.

nutrient_topic

Mangiferin research collection; topical membership is not evidence of a direct dietary effect. · Mangiferin

organism

Rattus norvegicus and cell-free chemistry

plain_language

Metal coordination altered protection of the redox buffer.

primary_references

[mangiferin-p17068204] Fe(III) shifts the mitochondria permeability transition-eliciting capacity of mangiferin to protection of organelle. (2007). https://pubmed.ncbi.nlm.nih.gov/17068204/ DOI: 10.1124/jpet.106.112003

tissue_or_cell_type

Isolated mitochondria

Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 757–768

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Iron-coordination spectroscopy and mitochondrial challenge · source_derived_draft · unverified_draft

### mangiferin-complex-gsh The ferric complex protected mitochondrial glutathione against oxidation. Condition category: normal nutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Metal coordination altered protection of the redox buffer. organism: Rattus norvegicus and cell-free chemistry tissue_or_cell_type: Isolated mitochondria experimental_model: Iron-coordination spectroscopy and mitochondrial challenge limitations: Defined chemical form and calcium context explain the different response; no clinical iron/mangiferin co-dosing recommendation. exposure: Assay-defined ferric iron-mangiferin complex evidence_span: {"source_cache": "artifacts/mangiferin-research/17068204.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d0b364cee6629228fe7bc41446a0e2ddfe62b9274d77d4781ca7439aedfbb64", "start_char": 0, "end_char": 1172, "text_sha256": "1d0b364cee6629228fe7bc41446a0e2ddfe62b9274d77d4781ca7439aedfbb64"} [mangiferin-p17068204] Fe(III) shifts the mitochondria permeability transition-eliciting capacity of mangiferin to protection of organelle. (2007). https://pubmed.ncbi.nlm.nih.gov/17068204/ DOI: 10.1124/jpet.106.112003

evidence_span

{"source_cache": "artifacts/mangiferin-research/38586992.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3568135f9e3471d748a1f42c7ed136800b1cb9d017ebd9aa1522de71b71a72be", "start_char": 0, "end_char": 1792, "text_sha256": "3568135f9e3471d748a1f42c7ed136800b1cb9d017ebd9aa1522de71b71a72be"}

experimental_model

Hydrogen-peroxide challenge with pharmacological HO-1 inhibition

exposure

Mangiferin before H2O2 exposure

limitations

Cell protection is not demonstrated retinal clinical efficacy; GPx isoforms unresolved and expression is not cofactor sufficiency.

nutrient_topic

Mangiferin research collection; topical membership is not evidence of a direct dietary effect. · Mangiferin

organism

Homo sapiens

plain_language

A cellular redox buffer was better maintained.

primary_references

[mangiferin-p38586992] Activation of Heme Oxygenase-1 by Mangiferin in Human Retinal Pigment Epithelial Cells Contributes to Blocking Oxidative Damage. (2024). https://pubmed.ncbi.nlm.nih.gov/38586992/ DOI: 10.4062/biomolther.2023.175

tissue_or_cell_type

ARPE-19 retinal pigment epithelial cells

Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 601–612

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Hydrogen-peroxide challenge with pharmacological HO-1 inhibition · source_derived_draft · unverified_draft

### mangiferin-rpe-gsh Mangiferin preserved the glutathione pool during H2O2 exposure. Condition category: normal nutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A cellular redox buffer was better maintained. organism: Homo sapiens tissue_or_cell_type: ARPE-19 retinal pigment epithelial cells experimental_model: Hydrogen-peroxide challenge with pharmacological HO-1 inhibition limitations: Cell protection is not demonstrated retinal clinical efficacy; GPx isoforms unresolved and expression is not cofactor sufficiency. exposure: Mangiferin before H2O2 exposure evidence_span: {"source_cache": "artifacts/mangiferin-research/38586992.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3568135f9e3471d748a1f42c7ed136800b1cb9d017ebd9aa1522de71b71a72be", "start_char": 0, "end_char": 1792, "text_sha256": "3568135f9e3471d748a1f42c7ed136800b1cb9d017ebd9aa1522de71b71a72be"} [mangiferin-p38586992] Activation of Heme Oxygenase-1 by Mangiferin in Human Retinal Pigment Epithelial Cells Contributes to Blocking Oxidative Damage. (2024). https://pubmed.ncbi.nlm.nih.gov/38586992/ DOI: 10.4062/biomolther.2023.175

evidence_span

{"source_cache": "artifacts/hbot-research/20055761.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3b9ac610e9510ed4f2fd2ed696009ab95dadac196fff3a7fe1644f03ed29d1dd", "start_char": 0, "end_char": 1322, "text_sha256": "3b9ac610e9510ed4f2fd2ed696009ab95dadac196fff3a7fe1644f03ed29d1dd"}

experimental_model

Enzyme assays of PHD2 and FIH with ascorbate, ascorbate analogues and alternative reducing agents

exposure

Prolyl and asparaginyl hydroxylation with and without ascorbate, glutathione or dithiothreitol

limitations

Purified-enzyme kinetics. It identifies which part of the ascorbate molecule matters, and shows other reductants substitute only partially.

nutrient_topic

Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

organism

Human enzymes

plain_language

It is one specific chemical group on vitamin C that does the job, and other reducing agents only half substitute.

primary_references

[hbot-p20055761] Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents. (2010). https://pubmed.ncbi.nlm.nih.gov/20055761/ DOI: 10.1042/bj20091609

tissue_or_cell_type

Purified enzyme with HIF-1alpha peptides

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 972–983

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme assays of PHD2 and FIH with ascorbate, ascorbate analogues and alternative reducing agents · source_derived_draft · unverified_draft

### hbot-ascorbate-ene-diol Replacing ascorbate with structural analogues showed that its side chain was not important for catalysis, whereas modifications to the ene-diol portion negated the ability to promote hydroxylation, and glutathione and dithiothreitol gave only partial, enzyme- and substrate-specific stimulation. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: It is one specific chemical group on vitamin C that does the job, and other reducing agents only half substitute. organism: Human enzymes tissue_or_cell_type: Purified enzyme with HIF-1alpha peptides experimental_model: Enzyme assays of PHD2 and FIH with ascorbate, ascorbate analogues and alternative reducing agents limitations: Purified-enzyme kinetics. It identifies which part of the ascorbate molecule matters, and shows other reductants substitute only partially. exposure: Prolyl and asparaginyl hydroxylation with and without ascorbate, glutathione or dithiothreitol evidence_span: {"source_cache": "artifacts/hbot-research/20055761.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3b9ac610e9510ed4f2fd2ed696009ab95dadac196fff3a7fe1644f03ed29d1dd", "start_char": 0, "end_char": 1322, "text_sha256": "3b9ac610e9510ed4f2fd2ed696009ab95dadac196fff3a7fe1644f03ed29d1dd"} [hbot-p20055761] Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents. (2010). https://pubmed.ncbi.nlm.nih.gov/20055761/ DOI: 10.1042/bj20091609

evidence_span

{"source_cache": "artifacts/hbot-research/15003734.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f", "start_char": 0, "end_char": 1432, "text_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f"}

experimental_model

Twelve patients sampled at the first and fifteenth hyperbaric session

exposure

Fifteen hyperbaric oxygen treatments without antioxidant supplementation

limitations

A small human series without a control group. The fall in enzyme activity may reflect oxidative modification of the enzymes themselves, which the authors state was still under investigation.

nutrient_topic

Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

organism

Human

plain_language

The selenium-dependent enzyme and the vitamin pools held steady while two other enzymes fell.

primary_references

[hbot-p15003734] Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen. (2004). https://pubmed.ncbi.nlm.nih.gov/15003734/ DOI: 10.1016/j.clinbiochem.2003.12.001

tissue_or_cell_type

Plasma and erythrocytes

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 270–281

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve patients sampled at the first and fifteenth hyperbaric session · source_derived_draft · unverified_draft

### hbot-gpx-unchanged Glutathione peroxidase activity remained almost unchanged, and no relevant differences were detected in reduced glutathione, alpha-tocopherol or retinol plasma levels. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The selenium-dependent enzyme and the vitamin pools held steady while two other enzymes fell. organism: Human tissue_or_cell_type: Plasma and erythrocytes experimental_model: Twelve patients sampled at the first and fifteenth hyperbaric session limitations: A small human series without a control group. The fall in enzyme activity may reflect oxidative modification of the enzymes themselves, which the authors state was still under investigation. exposure: Fifteen hyperbaric oxygen treatments without antioxidant supplementation evidence_span: {"source_cache": "artifacts/hbot-research/15003734.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f", "start_char": 0, "end_char": 1432, "text_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f"} [hbot-p15003734] Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen. (2004). https://pubmed.ncbi.nlm.nih.gov/15003734/ DOI: 10.1016/j.clinbiochem.2003.12.001

evidence_span

{"source_cache": "artifacts/hbot-research/15642322.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995", "start_char": 0, "end_char": 2646, "text_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995"}

experimental_model

Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR

exposure

99% oxygen at 50 atmospheres for 3 hours, then normal culture for up to 11 days

limitations

Fifty atmospheres is an extreme experimental exposure far above therapy, chosen to probe which defences matter. The selenoenzyme result is the informative part; the pressure is not clinically relevant.

nutrient_topic

Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

organism

Human cells

plain_language

Of all the defences measured, the selenium enzyme was the one that was knocked down.

primary_references

[hbot-p15642322] Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15642322/ DOI: 10.1016/j.exer.2004.07.001

tissue_or_cell_type

Lens epithelium

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 387–398

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR · source_derived_draft · unverified_draft

### hbot-trxr-activity-loss Thioredoxin reductase activity fell by 51% after the 3-hour oxygen exposure, while cellular glutathione and the activities of several other antioxidant enzymes, including glyceraldehyde-3-phosphate dehydrogenase, showed no immediate effect. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Of all the defences measured, the selenium enzyme was the one that was knocked down. organism: Human cells tissue_or_cell_type: Lens epithelium experimental_model: Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR limitations: Fifty atmospheres is an extreme experimental exposure far above therapy, chosen to probe which defences matter. The selenoenzyme result is the informative part; the pressure is not clinically relevant. exposure: 99% oxygen at 50 atmospheres for 3 hours, then normal culture for up to 11 days evidence_span: {"source_cache": "artifacts/hbot-research/15642322.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995", "start_char": 0, "end_char": 2646, "text_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995"} [hbot-p15642322] Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15642322/ DOI: 10.1016/j.exer.2004.07.001

evidence_access

Primary abstract

experimental_model

Wistar rat methylglyoxal model with GW9662 comparison.

limitations

GCL subunit-specific effects were not resolved in the accessed abstract.

nutrient_topic

Red yeast rice collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Red yeast rice

plain_language

The antioxidant-expression route was not blocked in the same way as the insulin endpoints.

primary_references

[23022408] Ankaflavin: a natural novel PPARγ agonist upregulates Nrf2 to attenuate methylglyoxal-induced diabetes in vivo. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23022408/ · DOI 10.1016/j.freeradbiomed.2012.09.025

Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 252–258

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Wistar rat methylglyoxal model with GW9662 comparison. · source_derived_draft · unverified_draft

## red-yeast-rice-ankaflavin-gcl The antioxidant-expression route was not blocked in the same way as the insulin endpoints. Ankaflavin increased hepatic GCL and HO-1 transcriptional activation; these effects persisted despite PPAR-gamma antagonist treatment. Model: Wistar rat methylglyoxal model with GW9662 comparison. Limitations: GCL subunit-specific effects were not resolved in the accessed abstract. Evidence access: Primary abstract [23022408] Ankaflavin: a natural novel PPARγ agonist upregulates Nrf2 to attenuate methylglyoxal-induced diabetes in vivo. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23022408/ · DOI 10.1016/j.freeradbiomed.2012.09.025

evidence_access

Primary abstract

experimental_model

Four-week Wistar rat model.

limitations

Does not establish dietary cysteine demand, human glutathione repletion or which flux caused the concentration change.

nutrient_topic

Red yeast rice collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Red yeast rice

plain_language

Glutathione connects this pigment to shared amino-acid-dependent defenses.

primary_references

[23022408] Ankaflavin: a natural novel PPARγ agonist upregulates Nrf2 to attenuate methylglyoxal-induced diabetes in vivo. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23022408/ · DOI 10.1016/j.freeradbiomed.2012.09.025

Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 260–266

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Four-week Wistar rat model. · source_derived_draft · unverified_draft

## red-yeast-rice-ankaflavin-gsh Glutathione connects this pigment to shared amino-acid-dependent defenses. Ankaflavin increased glutathione measured in liver and pancreas of methylglyoxal-treated rats. Model: Four-week Wistar rat model. Limitations: Does not establish dietary cysteine demand, human glutathione repletion or which flux caused the concentration change. Evidence access: Primary abstract [23022408] Ankaflavin: a natural novel PPARγ agonist upregulates Nrf2 to attenuate methylglyoxal-induced diabetes in vivo. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23022408/ · DOI 10.1016/j.freeradbiomed.2012.09.025

evidence_span

{"source_cache": "artifacts/chromium-research/36662348.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "500f334d72ca34561016a11f0c3bf866998ee364085855e54a2f29025bc916a8", "start_char": 0, "end_char": 1155, "text_sha256": "500f334d72ca34561016a11f0c3bf866998ee364085855e54a2f29025bc916a8"}

experimental_model

Characterization of pre-reacted chromium-ligand preparations and DNA-binding assays

exposure

Pre-reacted chromium cysteinate, chromium glutathione and chromium ascorbate preparations

limitations

These preparation-specific results challenge earlier assignments but do not show that Cr(VI) is harmless or directly reproduce every reductive chromate-DNA reaction.

nutrient_topic

Chromium research collection; topical membership is not evidence of a direct dietary effect. · Chromium

organism

Cell-free chemistry

plain_language

Pre-forming a metal complex can give a different result from reducing chromate in the presence of DNA; the claimed lesion identity needs checking.

primary_references

[chromium-p36662348] Examining the Potential Formation of Ternary DNA Complexes with Chromium‑Cysteine, Chromium-Ascorbate, and Chromium-Glutathione and Implications for Their Carcinogenicity. (2023). https://pubmed.ncbi.nlm.nih.gov/36662348/ DOI: 10.1007/s12011-023-03573-8

tissue_or_cell_type

Defined chromium complexes and DNA

Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 1186–1197

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Characterization of pre-reacted chromium-ligand preparations and DNA-binding assays · source_derived_draft · unverified_draft

### chromium-prereacted-dna-binding-null The characterized pre-reacted Cr(III)-cysteine, -glutathione and -ascorbate preparations did not measurably bind DNA or form the proposed ternary adducts under the tested conditions. Condition category: normal nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Pre-forming a metal complex can give a different result from reducing chromate in the presence of DNA; the claimed lesion identity needs checking. organism: Cell-free chemistry tissue_or_cell_type: Defined chromium complexes and DNA experimental_model: Characterization of pre-reacted chromium-ligand preparations and DNA-binding assays limitations: These preparation-specific results challenge earlier assignments but do not show that Cr(VI) is harmless or directly reproduce every reductive chromate-DNA reaction. exposure: Pre-reacted chromium cysteinate, chromium glutathione and chromium ascorbate preparations evidence_span: {"source_cache": "artifacts/chromium-research/36662348.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "500f334d72ca34561016a11f0c3bf866998ee364085855e54a2f29025bc916a8", "start_char": 0, "end_char": 1155, "text_sha256": "500f334d72ca34561016a11f0c3bf866998ee364085855e54a2f29025bc916a8"} [chromium-p36662348] Examining the Potential Formation of Ternary DNA Complexes with Chromium‑Cysteine, Chromium-Ascorbate, and Chromium-Glutathione and Implications for Their Carcinogenicity. (2023). https://pubmed.ncbi.nlm.nih.gov/36662348/ DOI: 10.1007/s12011-023-03573-8

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human K562 knockout, isotope tracing and controlled B6 culture conditions.

limitations

Tracing reflects pathway flux; it does not establish direct PLP transport by SLC25A38.

nutrient_topic

Glycine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Glycine

plain_language

A mitochondrial cofactor problem reduced the cell's ability to make glycine.

primary_references

SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39856062/ · DOI 10.1038/s41467-025-56130-3

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glycine: supply, one-carbon allocation, receptors and cross-nutrient mechanisms (2026-09-19) · lines 114–120

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human K562 knockout, isotope tracing and controlled B6 culture conditions. · source_derived_draft · unverified_draft

## glycine-s38-glycine-synthesis A mitochondrial cofactor problem reduced the cell's ability to make glycine. SLC25A38 loss reduced deuterated-serine incorporation into glycine and glycine-derived glutathione under low-B6 conditions. Model: Human K562 knockout, isotope tracing and controlled B6 culture conditions. Limitations: Tracing reflects pathway flux; it does not establish direct PLP transport by SLC25A38. Evidence access: Primary full text SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39856062/ · DOI 10.1038/s41467-025-56130-3

evidence_access

Primary abstract

experimental_model

Chemical assay with glutathione versus ascorbate conditions.

limitations

Not a measurement of GSH synthesis, recycling or depletion in humans.

nutrient_topic

Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol

plain_language

Glutathione changes the redox reaction rather than merely adding another antioxidant label.

primary_references

Effects of trans-resveratrol on copper-dependent hydroxyl-radical formation and DNA damage: evidence for hydroxyl-radical scavenging and a novel, glutathione-sparing mechanism of action. · 2000 · https://pubmed.ncbi.nlm.nih.gov/11032413/ · DOI 10.1006/abbi.2000.1973

Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 382–388

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Chemical assay with glutathione versus ascorbate conditions. · source_derived_draft · unverified_draft

## resveratrol-gsh-context Glutathione changes the redox reaction rather than merely adding another antioxidant label. In the glutathione-containing copper system, resveratrol reduced radical formation and glutathione-disulfide formation. Model: Chemical assay with glutathione versus ascorbate conditions. Limitations: Not a measurement of GSH synthesis, recycling or depletion in humans. Evidence access: Primary abstract Effects of trans-resveratrol on copper-dependent hydroxyl-radical formation and DNA damage: evidence for hydroxyl-radical scavenging and a novel, glutathione-sparing mechanism of action. · 2000 · https://pubmed.ncbi.nlm.nih.gov/11032413/ · DOI 10.1006/abbi.2000.1973

evidence_access

Primary abstract

experimental_model

Same four-week volunteer study.

limitations

Bilirubin was a surrogate; this was not a direct hepatic UGT flux measurement.

nutrient_topic

Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol

plain_language

A subgroup signal is not a universal detoxification effect.

primary_references

Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20716633/ · DOI 10.1158/1940-6207.CAPR-09-0155

Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 446–452

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same four-week volunteer study. · source_derived_draft · unverified_draft

## resveratrol-human-phase2 A subgroup signal is not a universal detoxification effect. Overall lymphocyte GST and bilirubin-based UGT1A1 indices changed minimally after resveratrol, with larger changes reported in low-baseline subgroups. Model: Same four-week volunteer study. Limitations: Bilirubin was a surrogate; this was not a direct hepatic UGT flux measurement. Evidence access: Primary abstract Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20716633/ · DOI 10.1158/1940-6207.CAPR-09-0155

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Curcumin analog chemistry and stimulated cellular NF-kappa-B assays

exposure

Curcumin, oxidation-resistant analogs and inhibition of glutathione biosynthesis

limitations

Mechanistic bioactivation evidence in experimental systems, not proof that every oral formulation inhibits human NF-kappa-B.

nutrient_topic

Curcumin research collection; topical membership is not evidence of a direct dietary effect. · Curcumin

organism

Cellular and purified-kinase systems; species not assigned from abstract

plain_language

Less protective buffering changed the response to the reactive compound.

primary_references

[curcumin-p29097552] The anti-inflammatory activity of curcumin is mediated by its oxidative metabolites. (2017). https://pubmed.ncbi.nlm.nih.gov/29097552/ DOI: 10.1074/jbc.ra117.000123

tissue_or_cell_type

Oxidative metabolite, protein-adduct and glutathione measurements

trigger_kind

machinery_impairment Imported condition classification; unverified.

Curcumin: metabolism, signaling and nutrient connections (2026-09-17) · lines 476–487

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Curcumin analog chemistry and stimulated cellular NF-kappa-B assays · source_derived_draft · unverified_draft

### curcumin-gsh-loss Inhibiting glutathione biosynthesis increased curcumin potency while reducing measured curcumin-glutathione adducts. Condition category: machinery_impairment nutrient_topic: Curcumin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less protective buffering changed the response to the reactive compound. organism: Cellular and purified-kinase systems; species not assigned from abstract tissue_or_cell_type: Oxidative metabolite, protein-adduct and glutathione measurements experimental_model: Curcumin analog chemistry and stimulated cellular NF-kappa-B assays limitations: Mechanistic bioactivation evidence in experimental systems, not proof that every oral formulation inhibits human NF-kappa-B. exposure: Curcumin, oxidation-resistant analogs and inhibition of glutathione biosynthesis evidence_span: {"source_cache": "artifacts/curcumin-research/29097552.publisher-preview.txt", "locator": "Primary public publisher preview, reference superscripts removed; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fe26fe4a94e0ab5b60d128b86deb5bc8723e13a0403fcbdba7ef97224a22ef9a", "start_char": 0, "end_char": 2711, "text_sha256": "fe26fe4a94e0ab5b60d128b86deb5bc8723e13a0403fcbdba7ef97224a22ef9a"} [curcumin-p29097552] The anti-inflammatory activity of curcumin is mediated by its oxidative metabolites. (2017). https://pubmed.ncbi.nlm.nih.gov/29097552/ DOI: 10.1074/jbc.ra117.000123

evidence_span

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experimental_model

Curcumin analog chemistry and stimulated cellular NF-kappa-B assays

exposure

NAC 3 mM overnight before the curcumin/LPS reporter assay

limitations

Cell assay, not evidence that oral NAC cancels curcumin benefits in people; enhanced glutathione buffering was the authors proposed this explanation.

nutrient_topic

Curcumin research collection; topical membership is not evidence of a direct dietary effect. · Curcumin

organism

Mus musculus

plain_language

A glutathione precursor changed the response in the opposite direction from blocking glutathione synthesis.

primary_references

[curcumin-p29097552] The anti-inflammatory activity of curcumin is mediated by its oxidative metabolites. (2017). https://pubmed.ncbi.nlm.nih.gov/29097552/ DOI: 10.1074/jbc.ra117.000123

tissue_or_cell_type

RAW264.7 macrophage-like cells

Curcumin: metabolism, signaling and nutrient connections (2026-09-17) · lines 489–500

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Curcumin analog chemistry and stimulated cellular NF-kappa-B assays · source_derived_draft · unverified_draft

### curcumin-nac-buffering NAC pretreatment shifted the curcumin dose-response curve toward lower inhibitory potency in RAW264.7 cells. Condition category: normal nutrient_topic: Curcumin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A glutathione precursor changed the response in the opposite direction from blocking glutathione synthesis. organism: Mus musculus tissue_or_cell_type: RAW264.7 macrophage-like cells experimental_model: Curcumin analog chemistry and stimulated cellular NF-kappa-B assays limitations: Cell assay, not evidence that oral NAC cancels curcumin benefits in people; enhanced glutathione buffering was the authors proposed this explanation. exposure: NAC 3 mM overnight before the curcumin/LPS reporter assay evidence_span: {"source_cache": "artifacts/curcumin-research/29097552.publisher-preview.txt", "locator": "Primary public publisher preview, reference superscripts removed; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fe26fe4a94e0ab5b60d128b86deb5bc8723e13a0403fcbdba7ef97224a22ef9a", "start_char": 0, "end_char": 2711, "text_sha256": "fe26fe4a94e0ab5b60d128b86deb5bc8723e13a0403fcbdba7ef97224a22ef9a"} [curcumin-p29097552] The anti-inflammatory activity of curcumin is mediated by its oxidative metabolites. (2017). https://pubmed.ncbi.nlm.nih.gov/29097552/ DOI: 10.1074/jbc.ra117.000123

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B2 supports a component of glutathione recycling; this is not proof of universal glutathione exhaustion.

experimental_model

Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions.

exposure

Red-cell age-fraction enzyme/cofactor assays, glutathione, hemoglobin species and peroxide susceptibility; observational comparison.

limitations

Observational age-fraction study; reduced glutathione itself was not among the significant between-group differences.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

A B2-dependent recycling enzyme was less active in red cells from the deficient group.

primary_references

[b2-powers1981] Riboflavin deficiency in man: effects on haemoglobin and reduced glutathione in erythrocytes of different ages (1981). https://pubmed.ncbi.nlm.nih.gov/7284295/ DOI: 10.1079/bjn19810031

tissue_or_cell_type

Human clinical setting

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1692–1703

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions. · source_derived_draft · unverified_draft

### b2-deficiency-redcell-gsr Marginally B2-deficient subjects had lower erythrocyte glutathione reductase activity than controls across the study comparison. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A B2-dependent recycling enzyme was less active in red cells from the deficient group. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions. limitations: Observational age-fraction study; reduced glutathione itself was not among the significant between-group differences. exposure: Red-cell age-fraction enzyme/cofactor assays, glutathione, hemoglobin species and peroxide susceptibility; observational comparison. cross_nutrient: B2 supports a component of glutathione recycling; this is not proof of universal glutathione exhaustion. [b2-powers1981] Riboflavin deficiency in man: effects on haemoglobin and reduced glutathione in erythrocytes of different ages (1981). https://pubmed.ncbi.nlm.nih.gov/7284295/ DOI: 10.1079/bjn19810031

cross_nutrient

B2-FAD supports GSH recycling; selenium-dependent GPX use of GSH is a separate reaction.

evidence_location

Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes

experimental_model

Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls.

exposure

Purified-enzyme assay

limitations

GSR is not glutathione peroxidase; this record does not show that B2 improves selenium repletion.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

This enzyme recycles glutathione after oxidation.

primary_references

[berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083

tissue_or_cell_type

Purified human GSR

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1332–1344

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls. · source_derived_draft · unverified_draft

### b2-gsr-gssg-to-gsh GSR reduces one glutathione-disulfide molecule to two reduced glutathione molecules using the NADPH/FAD catalytic relay. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This enzyme recycles glutathione after oxidation. organism: Homo sapiens tissue_or_cell_type: Purified human GSR experimental_model: Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls. limitations: GSR is not glutathione peroxidase; this record does not show that B2 improves selenium repletion. exposure: Purified-enzyme assay cross_nutrient: B2-FAD supports GSH recycling; selenium-dependent GPX use of GSH is a separate reaction. evidence_location: Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes [berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083

evidence_access

Primary abstract

experimental_model

Cultured human endothelial cells.

limitations

GSR expression does not establish increased flux or correction of riboflavin deficiency.

nutrient_topic

Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine

plain_language

This connects the response to glutathione recycling.

primary_references

Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049

Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 296–302

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cultured human endothelial cells. · source_derived_draft · unverified_draft

## ergothioneine-endothelial-gsr This connects the response to glutathione recycling. Ergothioneine increased glutathione reductase expression in human brain microvascular endothelial cells. Model: Cultured human endothelial cells. Limitations: GSR expression does not establish increased flux or correction of riboflavin deficiency. Evidence access: Primary abstract Uptake and protective effects of ergothioneine in human endothelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25022513/ · DOI 10.1124/jpet.114.214049

evidence_span

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experimental_model

Small crossover pharmacokinetic pilot in younger and older adults

exposure

500 mg R-lipoic acid versus 500 mg racemic lipoic acid

limitations

The indexed abstract does not specify reduced versus total glutathione assay pool; retain that uncertainty. A three-hour blood measurement is not a test of all intracellular pools.

nutrient_topic

Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid

organism

Human

plain_language

An acute blood measurement did not reproduce every cell-culture glutathione result.

primary_references

[ala-p22609537] Age and gender dependent bioavailability of R- and R,S-α-lipoic acid: a pilot study. (2012). https://pubmed.ncbi.nlm.nih.gov/22609537/ DOI: 10.1016/j.phrs.2012.05.002

tissue_or_cell_type

Plasma

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 676–687

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Small crossover pharmacokinetic pilot in younger and older adults · source_derived_draft · unverified_draft

### ala-acute-plasma-gsh-null Plasma glutathione did not change during the pilot’s three-hour sampling period. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: An acute blood measurement did not reproduce every cell-culture glutathione result. organism: Human tissue_or_cell_type: Plasma experimental_model: Small crossover pharmacokinetic pilot in younger and older adults limitations: The indexed abstract does not specify reduced versus total glutathione assay pool; retain that uncertainty. A three-hour blood measurement is not a test of all intracellular pools. exposure: 500 mg R-lipoic acid versus 500 mg racemic lipoic acid evidence_span: {"source_cache": "artifacts/ala-research/22609537.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bfd228f5a8102a99fecaf7c6de8d1cb910afacd695cb3947c60987f54da431fa", "start_char": 0, "end_char": 1645, "text_sha256": "bfd228f5a8102a99fecaf7c6de8d1cb910afacd695cb3947c60987f54da431fa"} [ala-p22609537] Age and gender dependent bioavailability of R- and R,S-α-lipoic acid: a pilot study. (2012). https://pubmed.ncbi.nlm.nih.gov/22609537/ DOI: 10.1016/j.phrs.2012.05.002

evidence_span

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experimental_model

Cell-culture thiol transport and glutathione experiments

exposure

Lipoic acid/DHLA treatment and extracellular thiol measurements

limitations

Cell-type and extracellular-substrate dependence; no demonstration of general methylation-vitamin depletion.

nutrient_topic

Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid

organism

Human, rat and mouse cells as specified

plain_language

The cells could import ready-to-use cysteine instead of relying on cystine uptake.

primary_references

[ala-p9288403] Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. (1997). https://pubmed.ncbi.nlm.nih.gov/9288403/ DOI: 10.1002/biof.5520060303

tissue_or_cell_type

Human lymphocytes, Jurkat cells and erythrocytes; rat C6 and mouse NB41A3 cells

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 806–817

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-culture thiol transport and glutathione experiments · source_derived_draft · unverified_draft

### ala-cysteine-gsh-route Increased extracellular cysteine supported cellular uptake and glutathione synthesis, bypassing dependence on cystine transport in the studied cells. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cells could import ready-to-use cysteine instead of relying on cystine uptake. organism: Human, rat and mouse cells as specified tissue_or_cell_type: Human lymphocytes, Jurkat cells and erythrocytes; rat C6 and mouse NB41A3 cells experimental_model: Cell-culture thiol transport and glutathione experiments limitations: Cell-type and extracellular-substrate dependence; no demonstration of general methylation-vitamin depletion. exposure: Lipoic acid/DHLA treatment and extracellular thiol measurements evidence_span: {"source_cache": "artifacts/ala-research/9288403.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2", "start_char": 0, "end_char": 1497, "text_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2"} [ala-p9288403] Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. (1997). https://pubmed.ncbi.nlm.nih.gov/9288403/ DOI: 10.1002/biof.5520060303

evidence_span

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experimental_model

Aging-rat liver biochemistry and R-lipoic-acid intervention

exposure

R-lipoic acid 40 mg/kg intraperitoneally; time course up to 48 hours

limitations

Animal injection study; changes in enzyme expression are distinct from direct radical scavenging and human clinical efficacy.

nutrient_topic

Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid

organism

Rat

plain_language

The liver increased part of its glutathione-making capacity.

primary_references

[ala-p14985508] Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. (2004). https://pubmed.ncbi.nlm.nih.gov/14985508/ DOI: 10.1073/pnas.0400282101

tissue_or_cell_type

Liver

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 858–869

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Aging-rat liver biochemistry and R-lipoic-acid intervention · source_derived_draft · unverified_draft

### ala-rla-gcl-rat R-lipoic-acid treatment increased GCLC and GCL activity at the later measured time point in aged rat liver. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The liver increased part of its glutathione-making capacity. organism: Rat tissue_or_cell_type: Liver experimental_model: Aging-rat liver biochemistry and R-lipoic-acid intervention limitations: Animal injection study; changes in enzyme expression are distinct from direct radical scavenging and human clinical efficacy. exposure: R-lipoic acid 40 mg/kg intraperitoneally; time course up to 48 hours evidence_span: {"source_cache": "artifacts/ala-research/14985508.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a43d83e66af102cc530c2cb2da20c79749ab5c85c815e573e9797f9fc6645d13", "start_char": 0, "end_char": 1696, "text_sha256": "a43d83e66af102cc530c2cb2da20c79749ab5c85c815e573e9797f9fc6645d13"} [ala-p14985508] Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. (2004). https://pubmed.ncbi.nlm.nih.gov/14985508/ DOI: 10.1073/pnas.0400282101

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Eight adults studied at clinical or environmental exposure levels; stable-isotope and metabolite assays.

limitations

Environmental-dose plasma DCA was undetectable; direct tissue-enzyme inhibition was inferred from metabolism, not biopsied. No low-dose equivalence is assumed.

nutrient_topic

L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine

plain_language

A drug metabolite can interfere with an amino-acid disposal enzyme.

primary_references

Chloral hydrate, through biotransformation to dichloroacetate, inhibits maleylacetoacetate isomerase and tyrosine catabolism in humans. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25283137/ · DOI 10.1515/dmdi-2014-0015

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 300–306

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Eight adults studied at clinical or environmental exposure levels; stable-isotope and metabolite assays. · source_derived_draft · unverified_draft

## l-tyrosine-chloral-gstz A drug metabolite can interfere with an amino-acid disposal enzyme. Five days of 1 g/day chloral hydrate produced detectable dichloroacetate and urinary maleylacetone in healthy volunteers, consistent with inhibition of GSTZ1/MAAI-dependent tyrosine catabolism. Model: Eight adults studied at clinical or environmental exposure levels; stable-isotope and metabolite assays. Limitations: Environmental-dose plasma DCA was undetectable; direct tissue-enzyme inhibition was inferred from metabolism, not biopsied. No low-dose equivalence is assumed. Evidence access: Primary abstract Chloral hydrate, through biotransformation to dichloroacetate, inhibits maleylacetoacetate isomerase and tyrosine catabolism in humans. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25283137/ · DOI 10.1515/dmdi-2014-0015

evidence_access

Primary abstract

experimental_model

Human MAAI crystal structure with glutathione and a substrate-mimicking sulfate ion.

limitations

Glutathione dependence does not imply stoichiometric depletion by ordinary tyrosine intake.

nutrient_topic

L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine

plain_language

Glutathione has a catalytic role in nutrient breakdown as well as antioxidant roles.

primary_references

Crystal structure of maleylacetoacetate isomerase/glutathione transferase zeta reveals the molecular basis for its remarkable catalytic promiscuity. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11327815/ · DOI 10.1021/bi002249z

L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 252–258

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human MAAI crystal structure with glutathione and a substrate-mimicking sulfate ion. · source_derived_draft · unverified_draft

## l-tyrosine-gst-isomerase Glutathione has a catalytic role in nutrient breakdown as well as antioxidant roles. Human GSTZ1/MAAI catalyzes glutathione-dependent isomerization of maleylacetoacetate to fumarylacetoacetate. Model: Human MAAI crystal structure with glutathione and a substrate-mimicking sulfate ion. Limitations: Glutathione dependence does not imply stoichiometric depletion by ordinary tyrosine intake. Evidence access: Primary abstract Crystal structure of maleylacetoacetate isomerase/glutathione transferase zeta reveals the molecular basis for its remarkable catalytic promiscuity. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11327815/ · DOI 10.1021/bi002249z

evidence_access

Primary abstract

experimental_model

Mouse macrophage metabolic manipulation and LPS stimulation.

limitations

IL-1beta transcription and inflammasome-mediated processing are different endpoints.

nutrient_topic

L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine

plain_language

An antioxidant-building pathway can support inflammatory gene expression.

primary_references

Serine Metabolism Supports Macrophage IL-1β Production. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30773464/ · DOI 10.1016/j.cmet.2019.01.014

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 230–236

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse macrophage metabolic manipulation and LPS stimulation. · source_derived_draft · unverified_draft

## l-serine-macrophage-gsh An antioxidant-building pathway can support inflammatory gene expression. Serine-derived glycine supported glutathione synthesis required for optimal LPS-induced IL-1beta mRNA expression; inflammasome activation was not the affected step. Model: Mouse macrophage metabolic manipulation and LPS stimulation. Limitations: IL-1beta transcription and inflammasome-mediated processing are different endpoints. Evidence access: Primary abstract Serine Metabolism Supports Macrophage IL-1β Production. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30773464/ · DOI 10.1016/j.cmet.2019.01.014

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human cancer-cell starvation with p53 comparisons.

limitations

The response depends on genotype and experimental conditions, not a universal ranking of serine uses.

nutrient_topic

L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine

plain_language

Cells can reallocate scarce substrate to survival rather than proliferation.

primary_references

Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23242140/ · DOI 10.1038/nature11743

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 198–204

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell starvation with p53 comparisons. · source_derived_draft · unverified_draft

## l-serine-starvation-p53 Cells can reallocate scarce substrate to survival rather than proliferation. Serine withdrawal induced a transient p53–p21 arrest that redirected limited serine toward glutathione synthesis and preserved antioxidant capacity in the tested human cancer cells. Model: Human cancer-cell starvation with p53 comparisons. Limitations: The response depends on genotype and experimental conditions, not a universal ranking of serine uses. Evidence access: Primary abstract Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23242140/ · DOI 10.1038/nature11743

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human cancer-cell p53 comparison, with an additional in-vivo tumor model.

limitations

This is not a proven dietary cancer therapy.

nutrient_topic

L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine

plain_language

The same shortage can have a different outcome when stress-response machinery is missing.

primary_references

Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23242140/ · DOI 10.1038/nature11743

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 206–212

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell p53 comparison, with an additional in-vivo tumor model. · source_derived_draft · unverified_draft

## l-serine-starvation-p53-loss The same shortage can have a different outcome when stress-response machinery is missing. p53-deficient cells failed to complete the adaptive response to serine withdrawal and developed oxidative stress, lower viability and impaired proliferation. Model: Human cancer-cell p53 comparison, with an additional in-vivo tumor model. Limitations: This is not a proven dietary cancer therapy. Evidence access: Primary abstract Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23242140/ · DOI 10.1038/nature11743

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human cell models; ROS probes, targeted redox sensors and serine isotope tracing.

limitations

The authors do not exclude effects during other physiological stresses; this is not a universal claim that mitochondrial NADPH is irrelevant to antioxidant defense.

nutrient_topic

L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline

plain_language

Losing this cofactor pool did not shut down every pathway that might be connected to it.

primary_references

Mitochondrial NADP(H) generation is essential for proline biosynthesis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888598/ · DOI 10.1126/science.abd5491

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 86–92

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cell models; ROS probes, targeted redox sensors and serine isotope tracing. · source_derived_draft · unverified_draft

## l-proline-nadk2-redox-boundary Losing this cofactor pool did not shut down every pathway that might be connected to it. Under the tested culture conditions, NADK2 deletion did not increase measured mitochondrial oxidative stress or disrupt mitochondrial folate pathway activity despite reduced proline synthesis. Model: Human cell models; ROS probes, targeted redox sensors and serine isotope tracing. Limitations: The authors do not exclude effects during other physiological stresses; this is not a universal claim that mitochondrial NADPH is irrelevant to antioxidant defense. Evidence access: Primary full text Mitochondrial NADP(H) generation is essential for proline biosynthesis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888598/ · DOI 10.1126/science.abd5491

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human RPE culture with pharmacological catabolism inhibition and metabolite measurements.

limitations

Pharmacological specificity and culture conditions limit inference; no human blood-proline threshold is established.

nutrient_topic

L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline

plain_language

A block in proline use can affect antioxidant production indirectly.

primary_references

Proline mediates metabolic communication between retinal pigment epithelial cells and the retina. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31110046/ · DOI 10.1074/jbc.RA119.007983

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 318–324

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human RPE culture with pharmacological catabolism inhibition and metabolite measurements. · source_derived_draft · unverified_draft

## l-proline-rpe-catabolism-block A block in proline use can affect antioxidant production indirectly. Blocking proline catabolism in human RPE impaired glucose metabolism and glutathione production. Model: Human RPE culture with pharmacological catabolism inhibition and metabolite measurements. Limitations: Pharmacological specificity and culture conditions limit inference; no human blood-proline threshold is established. Evidence access: Primary abstract Proline mediates metabolic communication between retinal pigment epithelial cells and the retina. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31110046/ · DOI 10.1074/jbc.RA119.007983

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse-cell transcription-factor silencing.

limitations

Baseline and oxidative-stress settings are distinct.

nutrient_topic

Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Fisetin

plain_language

Baseline glutathione regulation depended more on ATF4.

primary_references

Concurrent regulation of the transcription factors Nrf2 and ATF4 mediates the enhancement of glutathione levels by the flavonoid fisetin. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23618921/ · DOI 10.1016/j.bcp.2013.04.010

trigger_kind

machinery_impairment Imported condition classification; unverified.

Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 120–126

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse-cell transcription-factor silencing. · source_derived_draft · unverified_draft

## fisetin-atf4-basal-dependence Baseline glutathione regulation depended more on ATF4. ATF4 siRNA reduced the fisetin-associated basal glutathione increase; Nrf2 siRNA did not have the same basal requirement. Model: Mouse-cell transcription-factor silencing. Limitations: Baseline and oxidative-stress settings are distinct. Evidence access: Primary abstract Concurrent regulation of the transcription factors Nrf2 and ATF4 mediates the enhancement of glutathione levels by the flavonoid fisetin. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23618921/ · DOI 10.1016/j.bcp.2013.04.010

evidence_access

Primary full text

experimental_model

Rat model; H9c2 assays used 40 micromolar fisetin with 1 micromolar doxorubicin for 24 hours.

limitations

Does not establish selenium replacement or preservation of anticancer efficacy.

nutrient_topic

Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Fisetin

plain_language

A selenium-containing defense pathway accompanied protection.

primary_references

Fisetin Attenuates Doxorubicin-Induced Cardiomyopathy In Vivo and In Vitro by Inhibiting Ferroptosis Through SIRT1/Nrf2 Signaling Pathway Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/35273493/ · DOI 10.3389/fphar.2021.808480

Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 416–422

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat model; H9c2 assays used 40 micromolar fisetin with 1 micromolar doxorubicin for 24 hours. · source_derived_draft · unverified_draft

## fisetin-cardiac-gpx4 A selenium-containing defense pathway accompanied protection. Fisetin restored GPX4 protein and glutathione while reducing lipid-oxidation markers in doxorubicin-exposed rat hearts and H9c2 cells. Model: Rat model; H9c2 assays used 40 micromolar fisetin with 1 micromolar doxorubicin for 24 hours. Limitations: Does not establish selenium replacement or preservation of anticancer efficacy. Evidence access: Primary full text Fisetin Attenuates Doxorubicin-Induced Cardiomyopathy In Vivo and In Vitro by Inhibiting Ferroptosis Through SIRT1/Nrf2 Signaling Pathway Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/35273493/ · DOI 10.3389/fphar.2021.808480

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Rat cardiac-cell pharmacological inhibition.

limitations

Not proof that niacin or NAD supplements enhance fisetin.

nutrient_topic

Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Fisetin

plain_language

An intact regulatory pathway was required for the full response.

primary_references

Fisetin Attenuates Doxorubicin-Induced Cardiomyopathy In Vivo and In Vitro by Inhibiting Ferroptosis Through SIRT1/Nrf2 Signaling Pathway Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/35273493/ · DOI 10.3389/fphar.2021.808480

trigger_kind

machinery_impairment Imported condition classification; unverified.

Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 432–438

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat cardiac-cell pharmacological inhibition. · source_derived_draft · unverified_draft

## fisetin-cardiac-sirt1-block An intact regulatory pathway was required for the full response. SIRT1 inhibition attenuated fisetin protection in doxorubicin-exposed H9c2 cells and reduced the associated GSH/GPX4 response. Model: Rat cardiac-cell pharmacological inhibition. Limitations: Not proof that niacin or NAD supplements enhance fisetin. Evidence access: Primary abstract Fisetin Attenuates Doxorubicin-Induced Cardiomyopathy In Vivo and In Vitro by Inhibiting Ferroptosis Through SIRT1/Nrf2 Signaling Pathway Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/35273493/ · DOI 10.3389/fphar.2021.808480

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse cells; pharmacological GPX4 inhibition plus iron.

limitations

Not proof that fisetin worsens ordinary selenium deficiency; RSL3 and dietary selenium shortage differ.

nutrient_topic

Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Fisetin

plain_language

Protection can fail when a different defense step is blocked.

primary_references

Modulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33187316/ · DOI 10.3390/antiox9111113

trigger_kind

machinery_impairment Imported condition classification; unverified.

Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 168–174

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse cells; pharmacological GPX4 inhibition plus iron. · source_derived_draft · unverified_draft

## fisetin-gpx4-block-metal-injury Protection can fail when a different defense step is blocked. With RSL3-mediated GPX4 inhibition, 5 micromolar fisetin enhanced iron-potentiated HT22 toxicity at iron concentrations of 2.5 micromolar or higher. Model: Mouse cells; pharmacological GPX4 inhibition plus iron. Limitations: Not proof that fisetin worsens ordinary selenium deficiency; RSL3 and dietary selenium shortage differ. Evidence access: Primary full text Modulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33187316/ · DOI 10.3390/antiox9111113

evidence_access

Primary abstract

experimental_model

Purified human enzyme kinetics.

limitations

CDNB probe assay, not proven human chemosensitization or global detoxification failure.

nutrient_topic

Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Fisetin

plain_language

A compound that supports a glutathione pool can also inhibit an enzyme using it.

primary_references

The Interaction of the Flavonoid Fisetin with Human Glutathione Transferase A1-1. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33806779/ · DOI 10.3390/metabo11030190

Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 88–94

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human enzyme kinetics. · source_derived_draft · unverified_draft

## fisetin-gsta1-inhibition A compound that supports a glutathione pool can also inhibit an enzyme using it. Fisetin reversibly inhibited purified human GSTA1-1 with IC50 1.2 +/- 0.1 micromolar; inhibition was mixed toward glutathione and noncompetitive toward CDNB. Model: Purified human enzyme kinetics. Limitations: CDNB probe assay, not proven human chemosensitization or global detoxification failure. Evidence access: Primary abstract The Interaction of the Flavonoid Fisetin with Human Glutathione Transferase A1-1. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33806779/ · DOI 10.3390/metabo11030190

evidence_access

Primary full text

experimental_model

Mouse HT22 cells; separately added FeCl2/CuCl2, 0.5-10 micromolar.

limitations

Not a dietary deficiency experiment or evidence of systemic metal removal.

nutrient_topic

Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Fisetin

plain_language

Protection depended on the way oxidative stress was induced.

primary_references

Modulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33187316/ · DOI 10.3390/antiox9111113

Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 152–158

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse HT22 cells; separately added FeCl2/CuCl2, 0.5-10 micromolar. · source_derived_draft · unverified_draft

## fisetin-metal-gsh-protection Protection depended on the way oxidative stress was induced. At 5 micromolar, fisetin limited iron- or copper-potentiated glutathione loss and cell death in glutamate-challenged mouse HT22 cells. Model: Mouse HT22 cells; separately added FeCl2/CuCl2, 0.5-10 micromolar. Limitations: Not a dietary deficiency experiment or evidence of systemic metal removal. Evidence access: Primary full text Modulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33187316/ · DOI 10.3390/antiox9111113

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse-cell gene-silencing comparisons.

limitations

Cooperation in this assay is not proof of universal transcriptional synergy.

nutrient_topic

Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Fisetin

plain_language

The cell relies on both regulators during stress.

primary_references

Concurrent regulation of the transcription factors Nrf2 and ATF4 mediates the enhancement of glutathione levels by the flavonoid fisetin. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23618921/ · DOI 10.1016/j.bcp.2013.04.010

trigger_kind

machinery_impairment Imported condition classification; unverified.

Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 128–134

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse-cell gene-silencing comparisons. · source_derived_draft · unverified_draft

## fisetin-stress-cooperation The cell relies on both regulators during stress. Under oxidative stress, siRNA experiments implicated both Nrf2 and ATF4 in the mouse-cell glutathione response to fisetin. Model: Mouse-cell gene-silencing comparisons. Limitations: Cooperation in this assay is not proof of universal transcriptional synergy. Evidence access: Primary abstract Concurrent regulation of the transcription factors Nrf2 and ATF4 mediates the enhancement of glutathione levels by the flavonoid fisetin. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23618921/ · DOI 10.1016/j.bcp.2013.04.010

dose

Tartrazine 700 mg/kg body weight for 2 weeks

duration

2 treatment weeks; endpoint tissue analysis

evidence_access

Primary full-text methods/results and metadata.

evidence_scope

literature_reviewed; source-specific experimental curation

experimental_model

Male Wistar rats; six per group

limitations

Very high animal exposure. Results section reports lower ascorbic acid with no significant GSH or MDA change from tartrazine alone; broader abstract/discussion wording should not replace these results.

nutrient_topic

Tartrazine food-colorant chapter; nutrient, drug and peptide interactions retain their models and limits. · Tartrazine

organism

Male Wistar rats; six per group

plain_language

Tartrazine alone did not significantly change brain reduced glutathione relative to control rats.

primary_references

High-Dose Aspirin Reverses Tartrazine-Induced Cell Growth Dysregulation Independent of p53 Signaling and Antioxidant Mechanisms in Rat Brain. (2019). https://pubmed.ncbi.nlm.nih.gov/31032366/ DOI: 10.1155/2019/9096404

route

Oral tartrazine

tissue

Brain tissue biochemical and histological endpoints

Tartrazine: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 369–378

Original AI-assisted curation of eighteen primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Male Wistar rats; six per group · source_derived_draft · unverified_draft

## tartrazine-brain-gsh-null Tartrazine alone did not significantly change brain reduced glutathione relative to control rats. Model/species: Male Wistar rats; six per group Tissue: Brain tissue biochemical and histological endpoints Exposure: Tartrazine 700 mg/kg body weight for 2 weeks Route: Oral tartrazine Duration: 2 treatment weeks; endpoint tissue analysis Limits: Very high animal exposure. Results section reports lower ascorbic acid with no significant GSH or MDA change from tartrazine alone; broader abstract/discussion wording should not replace these results. Primary reference: High-Dose Aspirin Reverses Tartrazine-Induced Cell Growth Dysregulation Independent of p53 Signaling and Antioxidant Mechanisms in Rat Brain. (2019). https://pubmed.ncbi.nlm.nih.gov/31032366/ DOI: 10.1155/2019/9096404 Access: Primary full-text methods/results and metadata.

dose

Sulfanilic acid 1 micromolar-1 mM; mitochondrial depolarization reported at 1 mM

duration

Acute calcium time course; other assay intervals not specified in abstract

evidence_access

Primary PubMed abstract; unrecovered method details explicitly retained.

evidence_scope

literature_reviewed; source-specific experimental curation

experimental_model

Rat pancreatic AR42J cell line

limitations

The metabolite was administered directly. No measured oral tartrazine-to-pancreas exposure or pancreatitis outcome is established. Oxidant production was reported to be calcium-independent.

nutrient_topic

Tartrazine food-colorant chapter; nutrient, drug and peptide interactions retain their models and limits. · Tartrazine

organism

Rat pancreatic AR42J cell line

plain_language

Sulfanilic acid lowered the GSH/GSSG ratio in AR42J cells.

primary_references

Sulfanilic acid increases intracellular free-calcium concentration, induces reactive oxygen species production and impairs trypsin secretion in pancreatic AR42J cells. (2018). https://pubmed.ncbi.nlm.nih.gov/29986830/ DOI: 10.1016/j.fct.2018.07.001

route

In vitro metabolite exposure

tissue

Calcium, redox, mitochondrial and secretory assays

Tartrazine: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 160–169

Original AI-assisted curation of eighteen primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Rat pancreatic AR42J cell line · source_derived_draft · unverified_draft

## tartrazine-metabolite-gsh Sulfanilic acid lowered the GSH/GSSG ratio in AR42J cells. Model/species: Rat pancreatic AR42J cell line Tissue: Calcium, redox, mitochondrial and secretory assays Exposure: Sulfanilic acid 1 micromolar-1 mM; mitochondrial depolarization reported at 1 mM Route: In vitro metabolite exposure Duration: Acute calcium time course; other assay intervals not specified in abstract Limits: The metabolite was administered directly. No measured oral tartrazine-to-pancreas exposure or pancreatitis outcome is established. Oxidant production was reported to be calcium-independent. Primary reference: Sulfanilic acid increases intracellular free-calcium concentration, induces reactive oxygen species production and impairs trypsin secretion in pancreatic AR42J cells. (2018). https://pubmed.ncbi.nlm.nih.gov/29986830/ DOI: 10.1016/j.fct.2018.07.001 Access: Primary PubMed abstract; unrecovered method details explicitly retained.

evidence_span

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experimental_model

Tissue glutathione and covalent binding of tritiated metabolites in CD-1 mice and Sprague-Dawley rats

exposure

Intraperitoneal acetaminophen, with and without prior 3-methylcholanthrene induction

limitations

Compares two organs and two species in the same design. The authors note the covalent binding measurement is extremely sensitive to trace radiochemical impurity, which is an honest caution about the method.

nutrient_topic

Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. · Paracetamol

organism

Mouse and rat

plain_language

The drug empties the cell of its protective thiol and then sticks to proteins, most of all in mouse liver.

primary_references

[apap-p660552] Covalent binding of metabolites of acetaminophen to kidney protein and depletion of renal glutathione. (1978). https://pubmed.ncbi.nlm.nih.gov/660552/ DOI: 10.1016/s0022-3565(25)31316-9

tissue_or_cell_type

Liver, kidney cortex and renal papilla

Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 402–413

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Tissue glutathione and covalent binding of tritiated metabolites in CD-1 mice and Sprague-Dawley rats · source_derived_draft · unverified_draft

### apap-binding-tracks-glutathione-loss After intraperitoneal acetaminophen, tissue glutathione was reduced more in mice than in rats and more in liver than in kidney without appearance of oxidized glutathione in either tissue, covalent binding of tritiated metabolites to tissue protein was likewise greater in mice than rats and greater in liver than kidney, prior 3-methylcholanthrene produced far greater induced changes in liver than kidney suggesting the reactive metabolite forms by slightly different mechanisms in each organ, and at doses below those causing demonstrable acute toxicity the duration of covalent binding was longer for renal papilla than for renal cortex or liver. Condition category: normal nutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. plain_language: The drug empties the cell of its protective thiol and then sticks to proteins, most of all in mouse liver. organism: Mouse and rat tissue_or_cell_type: Liver, kidney cortex and renal papilla experimental_model: Tissue glutathione and covalent binding of tritiated metabolites in CD-1 mice and Sprague-Dawley rats limitations: Compares two organs and two species in the same design. The authors note the covalent binding measurement is extremely sensitive to trace radiochemical impurity, which is an honest caution about the method. exposure: Intraperitoneal acetaminophen, with and without prior 3-methylcholanthrene induction evidence_span: {"source_cache": "artifacts/paracetamol-research/660552.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7041ada7ee2ce923645d1103db3a3dccc3febcf138c5095e24aa96cdbc04e9e3", "start_char": 0, "end_char": 1309, "text_sha256": "7041ada7ee2ce923645d1103db3a3dccc3febcf138c5095e24aa96cdbc04e9e3"} [apap-p660552] Covalent binding of metabolites of acetaminophen to kidney protein and depletion of renal glutathione. (1978). https://pubmed.ncbi.nlm.nih.gov/660552/ DOI: 10.1016/s0022-3565(25)31316-9

evidence_span

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experimental_model

Ram seminal vesicle microsomal prostaglandin H synthase with product identification by cooxidation

exposure

Acetaminophen from 20 micromolar to above 10 millimolar, with glutathione, ascorbate and indomethacin

limitations

Shows that the drug both stimulates and inhibits the same enzyme depending on concentration, and that the enzyme makes NAPQI from it. A microsomal preparation at concentrations far above therapeutic.

nutrient_topic

Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. · Paracetamol

organism

Sheep

plain_language

The prostaglandin enzyme can itself turn the drug into the liver-damaging metabolite.

primary_references

[apap-p3124965] Acetaminophen and analogs as cosubstrates and inhibitors of prostaglandin H synthase. (1988). https://pubmed.ncbi.nlm.nih.gov/3124965/ DOI: 10.1016/0009-2797(88)90101-9

tissue_or_cell_type

Seminal vesicle microsomes

Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 129–140

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ram seminal vesicle microsomal prostaglandin H synthase with product identification by cooxidation · source_derived_draft · unverified_draft

### apap-the-enzyme-makes-napqi Using acetaminophen as a probe, at low concentrations it is converted in a cooxidation reaction with arachidonic acid to the dimer 4,4-dihydroxy-3,3-biacetanilide and other polymeric products, and the electrophilic metabolite N-acetyl-p-benzoquinone imine was detected directly and indirectly by its reaction with glutathione to form 3-S-glutathionylacetaminophen; the same products were formed by the synthase with hydrogen peroxide in reactions not inhibited by indomethacin, and formation of all products was inhibited by ascorbic acid and butylated hydroxyanisole. Condition category: normal nutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. plain_language: The prostaglandin enzyme can itself turn the drug into the liver-damaging metabolite. organism: Sheep tissue_or_cell_type: Seminal vesicle microsomes experimental_model: Ram seminal vesicle microsomal prostaglandin H synthase with product identification by cooxidation limitations: Shows that the drug both stimulates and inhibits the same enzyme depending on concentration, and that the enzyme makes NAPQI from it. A microsomal preparation at concentrations far above therapeutic. exposure: Acetaminophen from 20 micromolar to above 10 millimolar, with glutathione, ascorbate and indomethacin evidence_span: {"source_cache": "artifacts/paracetamol-research/3124965.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dcc85a1ab66984973092042b5553f43fbbe5eb10b674614c9b1fa991b3969502", "start_char": 0, "end_char": 2236, "text_sha256": "dcc85a1ab66984973092042b5553f43fbbe5eb10b674614c9b1fa991b3969502"} [apap-p3124965] Acetaminophen and analogs as cosubstrates and inhibitors of prostaglandin H synthase. (1988). https://pubmed.ncbi.nlm.nih.gov/3124965/ DOI: 10.1016/0009-2797(88)90101-9

cross_nutrient

true

evidence_location

Abstract; indexed primary Results summary

experimental_model

Purified human MMACHC; oxygen-controlled biochemical assay

exposure

GSH and specified B12 form under anaerobic versus aerobic conditions

limitations

Abstract-level extraction; stronger aerobic activity of the C. elegans enzyme must not be attributed to human MMACHC.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Homo sapiens

plain_language

Glutathione could supply reducing power, but oxygen strongly affected this human-protein reaction.

primary_references

[li-2014-gsh-electron] Glutathione-dependent one-electron transfer reactions catalyzed by a B12 trafficking protein (2014). https://pubmed.ncbi.nlm.nih.gov/24742678/ DOI: 10.1074/jbc.M114.567339

tissue_or_cell_type

Cell-free assay

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 767–779

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human MMACHC; oxygen-controlled biochemical assay · source_derived_draft · unverified_draft

### b12-human-gsh-decyanation Purified human CblC/MMACHC supported GSH-dependent decyanation of cyanocobalamin to cob(II)alamin efficiently under anaerobic conditions; the human reaction was oxygen-sensitive. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione could supply reducing power, but oxygen strongly affected this human-protein reaction. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Purified human MMACHC; oxygen-controlled biochemical assay limitations: Abstract-level extraction; stronger aerobic activity of the C. elegans enzyme must not be attributed to human MMACHC. exposure: GSH and specified B12 form under anaerobic versus aerobic conditions cross_nutrient: true evidence_location: Abstract; indexed primary Results summary [li-2014-gsh-electron] Glutathione-dependent one-electron transfer reactions catalyzed by a B12 trafficking protein (2014). https://pubmed.ncbi.nlm.nih.gov/24742678/ DOI: 10.1074/jbc.M114.567339

cross_nutrient

true

evidence_location

Abstract; indexed primary Results summary

experimental_model

Purified human MMACHC; oxygen-controlled biochemical assay

exposure

GSH and specified B12 form under anaerobic versus aerobic conditions

limitations

Abstract-level extraction; stronger aerobic activity of the C. elegans enzyme must not be attributed to human MMACHC.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Homo sapiens

plain_language

Glutathione could supply reducing power, but oxygen strongly affected this human-protein reaction.

primary_references

[li-2014-gsh-electron] Glutathione-dependent one-electron transfer reactions catalyzed by a B12 trafficking protein (2014). https://pubmed.ncbi.nlm.nih.gov/24742678/ DOI: 10.1074/jbc.M114.567339

tissue_or_cell_type

Cell-free assay

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 781–793

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human MMACHC; oxygen-controlled biochemical assay · source_derived_draft · unverified_draft

### b12-human-gsh-reduction Purified human CblC/MMACHC supported GSH-dependent reduction of aquocobalamin to cob(II)alamin efficiently under anaerobic conditions; the human reaction was oxygen-sensitive. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione could supply reducing power, but oxygen strongly affected this human-protein reaction. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Purified human MMACHC; oxygen-controlled biochemical assay limitations: Abstract-level extraction; stronger aerobic activity of the C. elegans enzyme must not be attributed to human MMACHC. exposure: GSH and specified B12 form under anaerobic versus aerobic conditions cross_nutrient: true evidence_location: Abstract; indexed primary Results summary [li-2014-gsh-electron] Glutathione-dependent one-electron transfer reactions catalyzed by a B12 trafficking protein (2014). https://pubmed.ncbi.nlm.nih.gov/24742678/ DOI: 10.1074/jbc.M114.567339

cross_nutrient

true

evidence_location

Primary abstract; indexed article Introduction/Figure 1

experimental_model

Purified human MMACHC substrate chemistry

exposure

Specified alkylcobalamin plus GSH; kinetic temperature 20 C

limitations

Reconstituted biochemical system; establishes reaction capability rather than the quantitatively dominant pathway in living humans.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Homo sapiens

plain_language

Glutathione receives the side group removed from this B12 form.

primary_references

[kim-2009-gsh-dealkylation] A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins (2009). https://pubmed.ncbi.nlm.nih.gov/19801555/ DOI: 10.1074/jbc.M109.057877

tissue_or_cell_type

Cell-free assay

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 725–737

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human MMACHC substrate chemistry · source_derived_draft · unverified_draft

### b12-mmachc-adenosyl-dealkylation Human MMACHC transfers the 5′-deoxyadenosyl group from adenosylcobalamin to glutathione, yielding cob(I)alamin and the corresponding glutathione thioether; reported turnover was 0.174 +/- 0.006 per hour at 20 C. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione receives the side group removed from this B12 form. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Purified human MMACHC substrate chemistry limitations: Reconstituted biochemical system; establishes reaction capability rather than the quantitatively dominant pathway in living humans. exposure: Specified alkylcobalamin plus GSH; kinetic temperature 20 C cross_nutrient: true evidence_location: Primary abstract; indexed article Introduction/Figure 1 [kim-2009-gsh-dealkylation] A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins (2009). https://pubmed.ncbi.nlm.nih.gov/19801555/ DOI: 10.1074/jbc.M109.057877

cross_nutrient

true

evidence_location

Primary abstract; indexed article Introduction/Figure 1

experimental_model

Purified human MMACHC substrate chemistry

exposure

Specified alkylcobalamin plus GSH; kinetic temperature 20 C

limitations

Reconstituted biochemical system; establishes reaction capability rather than the quantitatively dominant pathway in living humans.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Homo sapiens

plain_language

Glutathione receives the side group removed from this B12 form.

primary_references

[kim-2009-gsh-dealkylation] A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins (2009). https://pubmed.ncbi.nlm.nih.gov/19801555/ DOI: 10.1074/jbc.M109.057877

tissue_or_cell_type

Cell-free assay

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 711–723

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human MMACHC substrate chemistry · source_derived_draft · unverified_draft

### b12-mmachc-methyl-dealkylation Human MMACHC transfers the methyl group from methylcobalamin to glutathione, yielding cob(I)alamin and the corresponding glutathione thioether; reported turnover was 11.7 +/- 0.2 per hour at 20 C. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione receives the side group removed from this B12 form. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Purified human MMACHC substrate chemistry limitations: Reconstituted biochemical system; establishes reaction capability rather than the quantitatively dominant pathway in living humans. exposure: Specified alkylcobalamin plus GSH; kinetic temperature 20 C cross_nutrient: true evidence_location: Primary abstract; indexed article Introduction/Figure 1 [kim-2009-gsh-dealkylation] A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins (2009). https://pubmed.ncbi.nlm.nih.gov/19801555/ DOI: 10.1074/jbc.M109.057877

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

evidence_location

Results: Figure 5D; Experimental Procedures

experimental_model

Recombinant human proteins; blue-native PAGE

exposure

T182N versus matched delta123 comparator, MMACHC, MeCbl and GSH

limitations

Functional assay used human proteins; mouse MMADHC was used for the separate crystal structure. Truncation may affect full-length behavior.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Homo sapiens

plain_language

This variant disrupted the two processing proteins’ association.

primary_references

[froese-2015-complex] Structural Insights into the MMACHC-MMADHC Protein Complex Involved in Vitamin B12 Trafficking (2015). https://pubmed.ncbi.nlm.nih.gov/26483544/ DOI: 10.1074/jbc.M115.683268

tissue_or_cell_type

Cell-free assay

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 865–877

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human proteins; blue-native PAGE · source_derived_draft · unverified_draft

### b12-mmad-t182n-complex Human MMADHC delta123 carrying T182N showed strongly reduced complex formation with full-length human MMACHC after MeCbl/GSH incubation, compared with matched delta123 MMADHC. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This variant disrupted the two processing proteins’ association. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Recombinant human proteins; blue-native PAGE limitations: Functional assay used human proteins; mouse MMADHC was used for the separate crystal structure. Truncation may affect full-length behavior. exposure: T182N versus matched delta123 comparator, MMACHC, MeCbl and GSH cross_nutrient: false evidence_location: Results: Figure 5D; Experimental Procedures [froese-2015-complex] Structural Insights into the MMACHC-MMADHC Protein Complex Involved in Vitamin B12 Trafficking (2015). https://pubmed.ncbi.nlm.nih.gov/26483544/ DOI: 10.1074/jbc.M115.683268

evidence_span

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experimental_model

Chemotherapy-associated intestinal injury experiment

exposure

Cystine plus theanine during 5-fluorouracil exposure

limitations

Combination product, not isolated theanine. Preservation of antitumor activity in the tested model does not establish compatibility with every human chemotherapy regimen.

nutrient_topic

L-Theanine research collection; topical membership is not evidence of a direct dietary effect. · L-Theanine

organism

Mice

plain_language

This result belongs to the tested two-ingredient mixture and its chemotherapy context.

primary_references

[theanine-p34922485] Oral administration of cystine and theanine attenuates 5-fluorouracil-induced intestinal mucositis and diarrhea by suppressing both glutathione level decrease and ROS production in the small intestine of mucositis mouse model. (2021). https://pubmed.ncbi.nlm.nih.gov/34922485/ DOI: 10.1186/s12885-021-09057-z

tissue_or_cell_type

Intestinal redox balance and crypt injury

L-Theanine: metabolism, neural signaling, nutrient connections and human outcomes (2026-09-17) · lines 783–794

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chemotherapy-associated intestinal injury experiment · source_derived_draft · unverified_draft

### theanine-ct-diarrhea The cystine-theanine mixture reduced diarrhea in the mouse chemotherapy model. Condition category: normal nutrient_topic: L-Theanine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This result belongs to the tested two-ingredient mixture and its chemotherapy context. organism: Mice tissue_or_cell_type: Intestinal redox balance and crypt injury experimental_model: Chemotherapy-associated intestinal injury experiment limitations: Combination product, not isolated theanine. Preservation of antitumor activity in the tested model does not establish compatibility with every human chemotherapy regimen. exposure: Cystine plus theanine during 5-fluorouracil exposure evidence_span: {"source_cache": "artifacts/theanine-research/34922485.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5828410d2c083fec47a3c7e1907b801a2dc616dbbb7e5ed36e59d503bceeb282", "start_char": 0, "end_char": 1703, "text_sha256": "5828410d2c083fec47a3c7e1907b801a2dc616dbbb7e5ed36e59d503bceeb282"} [theanine-p34922485] Oral administration of cystine and theanine attenuates 5-fluorouracil-induced intestinal mucositis and diarrhea by suppressing both glutathione level decrease and ROS production in the small intestine of mucositis mouse model. (2021). https://pubmed.ncbi.nlm.nih.gov/34922485/ DOI: 10.1186/s12885-021-09057-z

evidence_span

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experimental_model

Chemotherapy-associated intestinal injury experiment

exposure

Cystine plus theanine during 5-fluorouracil exposure

limitations

Combination product, not isolated theanine. Preservation of antitumor activity in the tested model does not establish compatibility with every human chemotherapy regimen.

nutrient_topic

L-Theanine research collection; topical membership is not evidence of a direct dietary effect. · L-Theanine

organism

Mice

plain_language

This result belongs to the tested two-ingredient mixture and its chemotherapy context.

primary_references

[theanine-p34922485] Oral administration of cystine and theanine attenuates 5-fluorouracil-induced intestinal mucositis and diarrhea by suppressing both glutathione level decrease and ROS production in the small intestine of mucositis mouse model. (2021). https://pubmed.ncbi.nlm.nih.gov/34922485/ DOI: 10.1186/s12885-021-09057-z

tissue_or_cell_type

Intestinal redox balance and crypt injury

L-Theanine: metabolism, neural signaling, nutrient connections and human outcomes (2026-09-17) · lines 757–768

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chemotherapy-associated intestinal injury experiment · source_derived_draft · unverified_draft

### theanine-ct-redox The cystine-theanine mixture restored the intestinal GSH/GSSG ratio during 5-fluorouracil exposure. Condition category: normal nutrient_topic: L-Theanine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This result belongs to the tested two-ingredient mixture and its chemotherapy context. organism: Mice tissue_or_cell_type: Intestinal redox balance and crypt injury experimental_model: Chemotherapy-associated intestinal injury experiment limitations: Combination product, not isolated theanine. Preservation of antitumor activity in the tested model does not establish compatibility with every human chemotherapy regimen. exposure: Cystine plus theanine during 5-fluorouracil exposure evidence_span: {"source_cache": "artifacts/theanine-research/34922485.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5828410d2c083fec47a3c7e1907b801a2dc616dbbb7e5ed36e59d503bceeb282", "start_char": 0, "end_char": 1703, "text_sha256": "5828410d2c083fec47a3c7e1907b801a2dc616dbbb7e5ed36e59d503bceeb282"} [theanine-p34922485] Oral administration of cystine and theanine attenuates 5-fluorouracil-induced intestinal mucositis and diarrhea by suppressing both glutathione level decrease and ROS production in the small intestine of mucositis mouse model. (2021). https://pubmed.ncbi.nlm.nih.gov/34922485/ DOI: 10.1186/s12885-021-09057-z

evidence_span

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experimental_model

Chemotherapy-associated intestinal injury experiment

exposure

Cystine plus theanine during 5-fluorouracil exposure

limitations

Combination product, not isolated theanine. Preservation of antitumor activity in the tested model does not establish compatibility with every human chemotherapy regimen.

nutrient_topic

L-Theanine research collection; topical membership is not evidence of a direct dietary effect. · L-Theanine

organism

Mice

plain_language

This result belongs to the tested two-ingredient mixture and its chemotherapy context.

primary_references

[theanine-p34922485] Oral administration of cystine and theanine attenuates 5-fluorouracil-induced intestinal mucositis and diarrhea by suppressing both glutathione level decrease and ROS production in the small intestine of mucositis mouse model. (2021). https://pubmed.ncbi.nlm.nih.gov/34922485/ DOI: 10.1186/s12885-021-09057-z

tissue_or_cell_type

Intestinal redox balance and crypt injury

L-Theanine: metabolism, neural signaling, nutrient connections and human outcomes (2026-09-17) · lines 770–781

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chemotherapy-associated intestinal injury experiment · source_derived_draft · unverified_draft

### theanine-ct-ros The cystine-theanine mixture reduced reactive oxygen species in intestinal crypts. Condition category: normal nutrient_topic: L-Theanine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This result belongs to the tested two-ingredient mixture and its chemotherapy context. organism: Mice tissue_or_cell_type: Intestinal redox balance and crypt injury experimental_model: Chemotherapy-associated intestinal injury experiment limitations: Combination product, not isolated theanine. Preservation of antitumor activity in the tested model does not establish compatibility with every human chemotherapy regimen. exposure: Cystine plus theanine during 5-fluorouracil exposure evidence_span: {"source_cache": "artifacts/theanine-research/34922485.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5828410d2c083fec47a3c7e1907b801a2dc616dbbb7e5ed36e59d503bceeb282", "start_char": 0, "end_char": 1703, "text_sha256": "5828410d2c083fec47a3c7e1907b801a2dc616dbbb7e5ed36e59d503bceeb282"} [theanine-p34922485] Oral administration of cystine and theanine attenuates 5-fluorouracil-induced intestinal mucositis and diarrhea by suppressing both glutathione level decrease and ROS production in the small intestine of mucositis mouse model. (2021). https://pubmed.ncbi.nlm.nih.gov/34922485/ DOI: 10.1186/s12885-021-09057-z

evidence_access

Primary indexed abstract and figure descriptions.

experimental_model

Purified human sulfide:quinone oxidoreductase; transient kinetics and flavin spectroscopy.

interpretation_status

Source-derived research curation; not independent raw-data verification.

limitations

Enzyme-bound FAD is not extracellular FMN. This study did not test dietary B2 deficiency or combined B2 and ergothioneine treatment.

nutrient_topic

Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine

plain_language

Sulfur disposal has a flavin-dependent electron relay.

primary_references

Mishanina et al. Transient Kinetic Analysis of Hydrogen Sulfide Oxidation Catalyzed by Human Sulfide Quinone Oxidoreductase. DOI 10.1074/jbc.M115.682369; PMID 26318450; https://pubmed.ncbi.nlm.nih.gov/26318450/

source_locator

Abstract and Figure 1

Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 129–129

Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Purified human sulfide:quinone oxidoreductase; transient kinetics and flavin spectroscopy. · source_derived_draft · unverified_draft

Bound FAD cycles between reduction by sulfide and oxidation by ubiquinone during human SQOR catalysis.

evidence_access

Primary indexed abstract. Physiological acceptor assignment is a kinetic interpretation, not a direct measurement of flux in a patient.

experimental_model

Purified human SQOR in nanodiscs; steady-state and rapid-kinetic assays.

interpretation_status

Source-derived research curation; not independent raw-data verification.

limitations

Predominant acceptor is a kinetic interpretation; alternative acceptors can work in other assay conditions. Ergothioneine and nutrient depletion were not tested.

nutrient_topic

Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine

plain_language

Glutathione also participates in disposal of sulfide-derived sulfur.

primary_references

Landry et al. H2S oxidation by nanodisc-embedded human sulfide quinone oxidoreductase. DOI 10.1074/jbc.M117.788547; PMID 28512131; https://pubmed.ncbi.nlm.nih.gov/28512131/

source_locator

Abstract

Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 137–137

Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · Purified human SQOR in nanodiscs; steady-state and rapid-kinetic assays. · source_derived_draft · unverified_draft

Nanodisc-embedded human SQOR transferred sulfane sulfur to glutathione; kinetics supported GSH as the predominant physiological acceptor.

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Purified human enzyme; four modified cysteine residues; corroborating S-nitrosation detection in human cells and mouse tissues.

limitations

GSNO is not reduced glutathione; this exposure does not predict effects of oral glutathione. H2O2 resistance and GSNO sensitivity were distinct in this study.

nutrient_topic

L-Threonine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Threonine

plain_language

Chemical modification of the enzyme can disrupt loading and proofreading.

primary_references

Nitrosative stress inhibits aminoacylation and editing activities of mitochondrial threonyl-tRNA synthetase by S-nitrosation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32484546/ · DOI 10.1093/nar/gkaa471

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 90–96

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human enzyme; four modified cysteine residues; corroborating S-nitrosation detection in human cells and mouse tissues. · source_derived_draft · unverified_draft

## l-threonine-tars2-nitrosation Chemical modification of the enzyme can disrupt loading and proofreading. GSNO treatment S-nitrosated human mitochondrial ThrRS and reduced both aminoacylation and editing activity in vitro. Model: Purified human enzyme; four modified cysteine residues; corroborating S-nitrosation detection in human cells and mouse tissues. Limitations: GSNO is not reduced glutathione; this exposure does not predict effects of oral glutathione. H2O2 resistance and GSNO sensitivity were distinct in this study. Evidence access: Primary abstract Nitrosative stress inhibits aminoacylation and editing activities of mitochondrial threonyl-tRNA synthetase by S-nitrosation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32484546/ · DOI 10.1093/nar/gkaa471

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse cysteine repletion with or without dietary B5; subsequent tissue GSH/CoA and weight measurements.

limitations

A direct cross-nutrient repletion experiment in mice; not an established human treatment protocol. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

Restoring one nutrient repaired one branch but left another branch short of its other substrate.

primary_references

Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 324–330

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse cysteine repletion with or without dietary B5; subsequent tissue GSH/CoA and weight measurements. · source_derived_draft · unverified_draft

## l-cysteine-b5-blocks-coa-recovery Restoring one nutrient repaired one branch but left another branch short of its other substrate. After seven days of cysteine depletion, Cse-null mice repleted with cysteine but kept B5-deficient had persistently lower CoA and less weight recovery than mice receiving both nutrients, despite restored liver glutathione. Model: Mouse cysteine repletion with or without dietary B5; subsequent tissue GSH/CoA and weight measurements. Limitations: A direct cross-nutrient repletion experiment in mice; not an established human treatment protocol. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8 Evidence access: Primary full text Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse Cth deletion with controlled low cyst(e)ine feeding.

limitations

Genetic plus dietary intervention; this does not establish a dose threshold for healthy people.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

Diet became essential when the animal could not make enough internally.

primary_references

Cystathionine gamma-Lyase-deficient mice require dietary cysteine to protect against acute lethal myopathy and oxidative injury. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20566639/ · DOI 10.1074/jbc.M110.147439

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 300–306

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse Cth deletion with controlled low cyst(e)ine feeding. · source_derived_draft · unverified_draft

## l-cysteine-cth-diet-myopathy Diet became essential when the animal could not make enough internally. Cth-null mice on a low cyst(e)ine diet developed reduced liver/muscle glutathione, acute skeletal myopathy and fatal paralysis in the reported model. Model: Mouse Cth deletion with controlled low cyst(e)ine feeding. Limitations: Genetic plus dietary intervention; this does not establish a dose threshold for healthy people. Evidence access: Primary abstract Cystathionine gamma-Lyase-deficient mice require dietary cysteine to protect against acute lethal myopathy and oxidative injury. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20566639/ · DOI 10.1074/jbc.M110.147439

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse genetic/dietary depletion; tissue CoA measurements at days 2 and 7.

limitations

CoA depletion accompanies several changes; do not assign all weight loss to one metabolite. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

A cysteine shortage reduced an energy-metabolism cofactor as well as an antioxidant.

primary_references

Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 308–314

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse genetic/dietary depletion; tissue CoA measurements at days 2 and 7. · source_derived_draft · unverified_draft

## l-cysteine-depletion-coa A cysteine shortage reduced an energy-metabolism cofactor as well as an antioxidant. Combined Cse loss and cysteine-free feeding reduced liver and muscle CoA, alongside glutathione depletion and major metabolic changes. Model: Mouse genetic/dietary depletion; tissue CoA measurements at days 2 and 7. Limitations: CoA depletion accompanies several changes; do not assign all weight loss to one metabolite. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8 Evidence access: Primary full text Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Genetically engineered mice with established pancreatic tumors.

limitations

Not all tumors or normal tissues have the same dependency; dietary deprivation was not this intervention.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

A transporter dependency could be targeted in this animal cancer model.

primary_references

Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 228–234

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Genetically engineered mice with established pancreatic tumors. · source_derived_draft · unverified_draft

## l-cysteine-mouse-pdac-import-loss A transporter dependency could be targeted in this animal cancer model. Deleting Slc7a11 in established genetically engineered mouse PDAC induced tumor-selective ferroptosis and inhibited growth. Model: Genetically engineered mice with established pancreatic tumors. Limitations: Not all tumors or normal tissues have the same dependency; dietary deprivation was not this intervention. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

evidence_access

Primary abstract and primary figure descriptions

experimental_model

Purified human MPST kinetics; concentrations and acceptors varied.

limitations

Some small-thiol assays used millimolar concentrations; these are not demonstrated effects of oral cysteine or lipoic acid.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

Sharing a sulfur-transfer route does not make these acceptors equally effective inside cells.

primary_references

Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23698001/ · DOI 10.1074/jbc.M113.466177

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 460–466

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human MPST kinetics; concentrations and acceptors varied. · source_derived_draft · unverified_draft

## l-cysteine-mpst-acceptor-choice Sharing a sulfur-transfer route does not make these acceptors equally effective inside cells. Human MPST supported H2S production with thioredoxin and several low-molecular-weight acceptors, including cysteine, glutathione and dihydrolipoic acid. Model: Purified human MPST kinetics; concentrations and acceptors varied. Limitations: Some small-thiol assays used millimolar concentrations; these are not demonstrated effects of oral cysteine or lipoic acid. Evidence access: Primary abstract and primary figure descriptions Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23698001/ · DOI 10.1074/jbc.M113.466177

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse Slc1a1 deletion with NAC treatment.

limitations

NAC is the tested intervention, not free L-cysteine; no human cognitive benefit is established.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

A different precursor bypassed part of the uptake limitation in this animal model.

primary_references

Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16311588/ · DOI 10.1038/nn1609

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 108–114

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse Slc1a1 deletion with NAC treatment. · source_derived_draft · unverified_draft

## l-cysteine-nac-neuronal-rescue A different precursor bypassed part of the uptake limitation in this animal model. N-acetylcysteine treatment reversed reduced neuronal glutathione and oxidant-related abnormalities in EAAC1-deficient mice. Model: Mouse Slc1a1 deletion with NAC treatment. Limitations: NAC is the tested intervention, not free L-cysteine; no human cognitive benefit is established. Evidence access: Primary abstract Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16311588/ · DOI 10.1038/nn1609

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse EAAC1 gene deletion, hippocampal slices and aging observations.

limitations

Does not establish a human oral cysteine treatment or make neuronal and astrocytic transport interchangeable.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

A neuron can lack usable cysteine even when the amino acid exists elsewhere.

primary_references

Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16311588/ · DOI 10.1038/nn1609

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 100–106

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse EAAC1 gene deletion, hippocampal slices and aging observations. · source_derived_draft · unverified_draft

## l-cysteine-neuronal-uptake-gate A neuron can lack usable cysteine even when the amino acid exists elsewhere. Slc1a1-null mice had lower neuronal glutathione, increased oxidant susceptibility and age-dependent brain atrophy and behavioral changes. Model: Mouse EAAC1 gene deletion, hippocampal slices and aging observations. Limitations: Does not establish a human oral cysteine treatment or make neuronal and astrocytic transport interchangeable. Evidence access: Primary abstract Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16311588/ · DOI 10.1038/nn1609

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse knockout, zinc measurements and transient ischemia.

limitations

The experiment did not test dietary zinc deficiency or toxicity thresholds.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

Impaired cysteine supply affected metal handling as well as antioxidant capacity.

primary_references

EAAC1 gene deletion alters zinc homeostasis and exacerbates neuronal injury after transient cerebral ischemia. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21084597/ · DOI 10.1523/JNEUROSCI.2084-10.2010

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 116–122

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse knockout, zinc measurements and transient ischemia. · source_derived_draft · unverified_draft

## l-cysteine-neuronal-zinc-link Impaired cysteine supply affected metal handling as well as antioxidant capacity. EAAC1-null mice had increased vesicular/cytosolic hippocampal zinc and greater zinc redistribution and neuronal injury after transient cerebral ischemia. Model: Mouse knockout, zinc measurements and transient ischemia. Limitations: The experiment did not test dietary zinc deficiency or toxicity thresholds. Evidence access: Primary abstract EAAC1 gene deletion alters zinc homeostasis and exacerbates neuronal injury after transient cerebral ischemia. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21084597/ · DOI 10.1523/JNEUROSCI.2084-10.2010

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse EAAC1-null ischemia model.

limitations

NAC and chelators are separate interventions; the study does not show that extra dietary cysteine and zinc are synergistic.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

Restoring precursor supply and binding excess labile zinc were distinct rescue routes.

primary_references

EAAC1 gene deletion alters zinc homeostasis and exacerbates neuronal injury after transient cerebral ischemia. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21084597/ · DOI 10.1523/JNEUROSCI.2084-10.2010

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 124–130

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse EAAC1-null ischemia model. · source_derived_draft · unverified_draft

## l-cysteine-neuronal-zinc-rescue Restoring precursor supply and binding excess labile zinc were distinct rescue routes. NAC restored neuronal glutathione and normalized basal zinc levels in EAAC1-null mice; NAC or zinc chelation reduced ischemia-associated zinc movement, superoxide and neuronal death. Model: Mouse EAAC1-null ischemia model. Limitations: NAC and chelators are separate interventions; the study does not show that extra dietary cysteine and zinc are synergistic. Evidence access: Primary abstract EAAC1 gene deletion alters zinc homeostasis and exacerbates neuronal injury after transient cerebral ischemia. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21084597/ · DOI 10.1523/JNEUROSCI.2084-10.2010

evidence_access

Primary full text

experimental_model

Human PDAC stable-isotope tracing.

limitations

No labeling of taurine, lactate, citrate or glutamate was detected in these assays; that does not abolish those routes in other tissues.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

Cysteine-derived material entered more than one protective metabolic pool.

primary_references

Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 188–194

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC stable-isotope tracing. · source_derived_draft · unverified_draft

## l-cysteine-pdac-carbon-tracing Cysteine-derived material entered more than one protective metabolic pool. Carbon-13 cystine tracing showed labeling of glutathione and CoA over the experiment, including CoA labeling over 24 hours. Model: Human PDAC stable-isotope tracing. Limitations: No labeling of taurine, lactate, citrate or glutamate was detected in these assays; that does not abolish those routes in other tissues. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human pancreatic cancer cultures; nutrient withdrawal, oxidation and viability assays.

limitations

Culture starvation is not dietary treatment; one of the tested lines differed.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

Dependence on external sulfur varied between cancer-cell models.

primary_references

Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 180–186

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human pancreatic cancer cultures; nutrient withdrawal, oxidation and viability assays. · source_derived_draft · unverified_draft

## l-cysteine-pdac-cystine-withdrawal Dependence on external sulfur varied between cancer-cell models. Cystine starvation induced lipid oxidation and ferroptosis in four of five tested human PDAC cell lines. Model: Human pancreatic cancer cultures; nutrient withdrawal, oxidation and viability assays. Limitations: Culture starvation is not dietary treatment; one of the tested lines differed. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human PDAC culture; pharmacological PANKi/BSO combination.

limitations

This is a demonstrated drug-combination interaction in this assay, not evidence for oral B5/cysteine supplement synergy.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

Two protective branches were experimentally blocked together.

primary_references

Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 212–218

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC culture; pharmacological PANKi/BSO combination. · source_derived_draft · unverified_draft

## l-cysteine-pdac-dual-block Two protective branches were experimentally blocked together. Pantothenate-kinase inhibition combined with BSO synergistically induced ferroptosis in the reported PDAC assays. Model: Human PDAC culture; pharmacological PANKi/BSO combination. Limitations: This is a demonstrated drug-combination interaction in this assay, not evidence for oral B5/cysteine supplement synergy. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human PDAC cultures, BSO and viability/lipid-ROS assays.

limitations

This null result is model-specific; it does not make glutathione dispensable in general.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

Loss of glutathione alone did not explain the whole cysteine-depletion effect.

primary_references

Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 204–210

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC cultures, BSO and viability/lipid-ROS assays. · source_derived_draft · unverified_draft

## l-cysteine-pdac-gsh-only-limit Loss of glutathione alone did not explain the whole cysteine-depletion effect. Buthionine sulfoximine lowered glutathione without inducing lipid oxidation or loss of viability under the tested PDAC conditions. Model: Human PDAC cultures, BSO and viability/lipid-ROS assays. Limitations: This null result is model-specific; it does not make glutathione dispensable in general. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human HEK293 metabolic tracing and enzyme perturbation.

limitations

Compensation requires intact transsulfuration and does not prove that B6 supplementation rescues every transport defect.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

An internal synthesis route compensated when imported cystine was harder to use.

primary_references

TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 76–82

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HEK293 metabolic tracing and enzyme perturbation. · source_derived_draft · unverified_draft

## l-cysteine-trp14-compensation An internal synthesis route compensated when imported cystine was harder to use. TXNDC17 knockout shifted human-cell cysteine supply toward transsulfuration, as assessed using labeled methionine and downstream sulfur metabolites. Model: Human HEK293 metabolic tracing and enzyme perturbation. Limitations: Compensation requires intact transsulfuration and does not prove that B6 supplementation rescues every transport defect. Evidence access: Primary full text TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1

evidence_access

Primary abstract

experimental_model

Human endothelial-cell enzyme-activity assay.

limitations

The assay does not resolve the GPX isoform, demonstrate selenium repletion, or quantify glutathione synthesis.

nutrient_topic

Astaxanthin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Astaxanthin

plain_language

The antioxidant enzyme response changed as well.

primary_references

Astaxanthin Induces the Nrf2/HO-1 Antioxidant Pathway in Human Umbilical Vein Endothelial Cells by Generating Trace Amounts of ROS. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29381356/ · DOI 10.1021/acs.jafc.7b05493

Astaxanthin: transport, membrane chemistry, signaling and nutrient interactions (2026-09-19) · lines 238–244

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human endothelial-cell enzyme-activity assay. · source_derived_draft · unverified_draft

## astaxanthin-gpx-activity The antioxidant enzyme response changed as well. Astaxanthin increased measured glutathione-peroxidase activity in the HUVEC experiment. Model: Human endothelial-cell enzyme-activity assay. Limitations: The assay does not resolve the GPX isoform, demonstrate selenium repletion, or quantify glutathione synthesis. Evidence access: Primary abstract Astaxanthin Induces the Nrf2/HO-1 Antioxidant Pathway in Human Umbilical Vein Endothelial Cells by Generating Trace Amounts of ROS. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29381356/ · DOI 10.1021/acs.jafc.7b05493

evidence_span

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experimental_model

Metabolite exposure and gene/protein/redox measurements

exposure

Time- and dose-dependent apo-10-prime-lycopenoid exposure

limitations

Cell-culture metabolite results do not prove oral lycopene reaches equivalent tissue concentrations or prevents human cancer.

nutrient_topic

Lycopene research collection; topical membership is not evidence of a direct dietary effect. · Lycopene

organism

Human BEAS-2B bronchial epithelial cells

plain_language

A measured glutathione pool rose; this does not show that dietary precursors were sufficient in every tissue.

primary_references

[lycopene-p18566994] Enzymatic metabolites of lycopene induce Nrf2-mediated expression of phase II detoxifying/antioxidant enzymes in human bronchial epithelial cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18566994/ DOI: 10.1002/ijc.23696

tissue_or_cell_type

Nucleus, antioxidant enzymes and intracellular glutathione

Lycopene: absorption, metabolism, nutrient connections and human outcomes (2026-09-17) · lines 559–570

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolite exposure and gene/protein/redox measurements · source_derived_draft · unverified_draft

### lycopene-apo-glutathione The metabolite increased total intracellular glutathione in BEAS-2B cells. Condition category: normal nutrient_topic: Lycopene research collection; topical membership is not evidence of a direct dietary effect. plain_language: A measured glutathione pool rose; this does not show that dietary precursors were sufficient in every tissue. organism: Human BEAS-2B bronchial epithelial cells tissue_or_cell_type: Nucleus, antioxidant enzymes and intracellular glutathione experimental_model: Metabolite exposure and gene/protein/redox measurements limitations: Cell-culture metabolite results do not prove oral lycopene reaches equivalent tissue concentrations or prevents human cancer. exposure: Time- and dose-dependent apo-10-prime-lycopenoid exposure evidence_span: {"source_cache": "artifacts/lycopene-research/18566994.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e34a21bb159c3e48372fd5cb104bfa50572903a5ef168b10100976a718b7b534", "start_char": 0, "end_char": 1416, "text_sha256": "e34a21bb159c3e48372fd5cb104bfa50572903a5ef168b10100976a718b7b534"} [lycopene-p18566994] Enzymatic metabolites of lycopene induce Nrf2-mediated expression of phase II detoxifying/antioxidant enzymes in human bronchial epithelial cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18566994/ DOI: 10.1002/ijc.23696

evidence_access

Primary abstract

experimental_model

Biochemical catecholaldehyde comparisons.

limitations

No universal antioxidant ranking follows.

nutrient_topic

Carnosine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnosine / beta-alanyl-L-histidine

plain_language

Different scavengers favor different aldehydes.

primary_references

Biochemical characterization of the catecholaldehyde reactivity of L-carnosine and its therapeutic potential in human myocardium. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30191330/ · DOI 10.1007/s00726-018-2647-y

Carnosine: synthesis, transport, carbonyl chemistry and nutrient interactions (2026-09-19) · lines 276–282

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Biochemical catecholaldehyde comparisons. · source_derived_draft · unverified_draft

## carnosine-dopal Different scavengers favor different aldehydes. Carnosine reacted with DOPAL and DOPEGAL; glutathione showed little DOPAL reactivity under the tested conditions. Model: Biochemical catecholaldehyde comparisons. Limitations: No universal antioxidant ranking follows. Evidence access: Primary abstract Biochemical characterization of the catecholaldehyde reactivity of L-carnosine and its therapeutic potential in human myocardium. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30191330/ · DOI 10.1007/s00726-018-2647-y

evidence_access

Primary abstract

experimental_model

Atrial tissue from cardiac-surgery patients, ex vivo.

limitations

No oral intervention or clinical cardiac benefit established.

nutrient_topic

Carnosine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnosine / beta-alanyl-L-histidine

plain_language

A chemical difference translated into protection in sampled heart tissue.

primary_references

Biochemical characterization of the catecholaldehyde reactivity of L-carnosine and its therapeutic potential in human myocardium. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30191330/ · DOI 10.1007/s00726-018-2647-y

Carnosine: synthesis, transport, carbonyl chemistry and nutrient interactions (2026-09-19) · lines 292–298

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Atrial tissue from cardiac-surgery patients, ex vivo. · source_derived_draft · unverified_draft

## carnosine-human-heart-respiration A chemical difference translated into protection in sampled heart tissue. Carnosine pretreatment attenuated DOPAL suppression of ADP-stimulated respiration in permeabilized human atrial fibers; GSH and cysteine did not. Model: Atrial tissue from cardiac-surgery patients, ex vivo. Limitations: No oral intervention or clinical cardiac benefit established. Evidence access: Primary abstract Biochemical characterization of the catecholaldehyde reactivity of L-carnosine and its therapeutic potential in human myocardium. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30191330/ · DOI 10.1007/s00726-018-2647-y

evidence_span

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experimental_model

Winter swimmers compared with people who had never taken part, sampled for erythrocyte and plasma antioxidants

exposure

Habitual ice bathing

limitations

A cross-sectional comparison, so self-selection cannot be excluded. The authors frame it as adaptation to repeated oxidative stress.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Human

plain_language

People who swim in ice water carry more antioxidant defence at rest.

primary_references

[cold-p10396606] Improved antioxidative protection in winter swimmers. (1999). https://pubmed.ncbi.nlm.nih.gov/10396606/ DOI: 10.1093/qjmed/92.4.193

tissue_or_cell_type

Erythrocytes and plasma

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 689–700

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Winter swimmers compared with people who had never taken part, sampled for erythrocyte and plasma antioxidants · source_derived_draft · unverified_draft

### cold-winter-swimmer-antioxidants Baseline reduced glutathione concentration and erythrocyte superoxide dismutase and catalase activities were higher in winter swimmers than in controls, which the authors interpret as an adaptive response to repeated oxidative stress and postulate as a mechanism of increased tolerance to environmental stress. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: People who swim in ice water carry more antioxidant defence at rest. organism: Human tissue_or_cell_type: Erythrocytes and plasma experimental_model: Winter swimmers compared with people who had never taken part, sampled for erythrocyte and plasma antioxidants limitations: A cross-sectional comparison, so self-selection cannot be excluded. The authors frame it as adaptation to repeated oxidative stress. exposure: Habitual ice bathing evidence_span: {"source_cache": "artifacts/cold-research/10396606.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fdd2deec82fad8f9e148848c443d5b173ec42c0e07d9045c59773f7109883a7b", "start_char": 0, "end_char": 1139, "text_sha256": "fdd2deec82fad8f9e148848c443d5b173ec42c0e07d9045c59773f7109883a7b"} [cold-p10396606] Improved antioxidative protection in winter swimmers. (1999). https://pubmed.ncbi.nlm.nih.gov/10396606/ DOI: 10.1093/qjmed/92.4.193

evidence_access

Primary full text; Figure 5

experimental_model

Caco-2 co-exposure experiments.

limitations

Not evidence that NAC supplements prevent effects of dietary aspartame.

nutrient_topic

Aspartame collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Aspartame

plain_language

An antioxidant-related perturbation changed the pathway response.

primary_references

Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32580504/ · DOI 10.3390/nu12061862

Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20) · lines 226–232

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Caco-2 co-exposure experiments. · source_derived_draft · unverified_draft

## aspartame-nac-rescue An antioxidant-related perturbation changed the pathway response. N-acetylcysteine at 1 mM attenuated aspartame-associated oxidative and barrier changes. Model: Caco-2 co-exposure experiments. Limitations: Not evidence that NAC supplements prevent effects of dietary aspartame. Evidence access: Primary full text; Figure 5 Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32580504/ · DOI 10.3390/nu12061862

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Neuronal hybrid-cell nutrient-withdrawal experiment.

limitations

The deficient precursor is cystine/cysteine supply, not glutamate; no human dietary threshold is established.

nutrient_topic

L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate

plain_language

Removing the missing precursor reproduced the supply failure.

primary_references

Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2576375/ · DOI 10.1016/0896-6273(89)90043-3

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 346–352

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Neuronal hybrid-cell nutrient-withdrawal experiment. · source_derived_draft · unverified_draft

## glutamate-cystine-shortage Removing the missing precursor reproduced the supply failure. Lowering culture-medium cystine mimicked glutamate-associated glutathione loss and oxidative cytotoxicity in N18-RE-105 cells. Model: Neuronal hybrid-cell nutrient-withdrawal experiment. Limitations: The deficient precursor is cystine/cysteine supply, not glutamate; no human dietary threshold is established. Evidence access: Primary abstract Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2576375/ · DOI 10.1016/0896-6273(89)90043-3

evidence_access

Primary abstract

experimental_model

Neuronal hybrid-cell transport, glutathione and peroxide assays.

limitations

A specific experimental toxicity mechanism is retained without inferring normal food-related brain injury.

nutrient_topic

L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate

plain_language

Oxidative injury arose through precursor supply, a different route from opening an excitatory receptor.

primary_references

Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2576375/ · DOI 10.1016/0896-6273(89)90043-3

L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 338–344

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Neuronal hybrid-cell transport, glutathione and peroxide assays. · source_derived_draft · unverified_draft

## glutamate-extracellular-gsh-loss Oxidative injury arose through precursor supply, a different route from opening an excitatory receptor. Extracellular glutamate exposure lowered glutathione and increased intracellular peroxides in N18-RE-105 cells alongside inhibited cystine uptake. Model: Neuronal hybrid-cell transport, glutathione and peroxide assays. Limitations: A specific experimental toxicity mechanism is retained without inferring normal food-related brain injury. Evidence access: Primary abstract Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2576375/ · DOI 10.1016/0896-6273(89)90043-3

access_level

abstract_only

compartment

Mitochondrial GSH versus intracellular GSH distinguished by authors

dose

Unknown: full methods unavailable

duration

Unknown: full methods unavailable

endpoint

mitochondrial-gsh-import

evidence_location

Primary indexed abstract; experiment-specific methods unavailable

experimental_model

Protein interaction/stability, knockdown and compound experiments reported in abstract

exposure

dlat

limitations

ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. Mechanistic interpretation reported in abstract; mediation/rescue controls cannot be assessed without full text.

nutrient_topic

Topical cross-reference only; no inheritance of another actor's effects. · GSH

organism

Human colorectal cancer models; individual experiments require full-text confirmation

plain_language

The authors connect DLAT-associated transporter stabilization with maintained mitochondrial glutathione import.

primary_locator

[{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}]

primary_references

https://doi.org/10.1016/j.freeradbiomed.2026.04.133

tissue_or_cell_type

Colorectal cancer models; claim-specific cell line not established from abstract

DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 750–764

AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Protein interaction/stability, knockdown and compound experiments reported in abstract · source_derived_draft · unverified_draft

The authors connect DLAT-associated transporter stabilization with maintained mitochondrial glutathione import. organism: Human colorectal cancer models; individual experiments require full-text confirmation tissue_or_cell_type: Colorectal cancer models; claim-specific cell line not established from abstract experimental_model: Protein interaction/stability, knockdown and compound experiments reported in abstract compartment: Mitochondrial GSH versus intracellular GSH distinguished by authors dose: Unknown: full methods unavailable duration: Unknown: full methods unavailable primary_references: https://doi.org/10.1016/j.freeradbiomed.2026.04.133 access_level: abstract_only evidence_location: Primary indexed abstract; experiment-specific methods unavailable endpoint: mitochondrial-gsh-import exposure: dlat limitations: ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. Mechanistic interpretation reported in abstract; mediation/rescue controls cannot be assessed without full text. primary_locator: [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}] plain_language: The authors connect DLAT-associated transporter stabilization with maintained mitochondrial glutathione import.

dose

Indicaxanthin 60 micromolar with cisplatin 10 micromolar; individual-agent controls

duration

24 h

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human HeLa cervical cancer cells

limitations

Cell-culture chemosensitization is not clinical cancer efficacy. Redox-probe signals and protein changes do not prove direct target binding. Glutathione was assessed with CMFDA fluorescence; the result does not establish an isolated block of synthesis.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human HeLa cervical cancer cells

plain_language

Indicaxanthin plus cisplatin lowered the glutathione-associated signal more than cisplatin alone in HeLa cells.

primary_references

The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis. (2020). https://pubmed.ncbi.nlm.nih.gov/32630700/ DOI: 10.3390/biom10070994

route

In vitro co-treatment

tissue

Cell death and redox assays

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 294–303

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human HeLa cervical cancer cells · source_derived_draft · unverified_draft

## indicaxanthin-cisplatin-gsh Indicaxanthin plus cisplatin lowered the glutathione-associated signal more than cisplatin alone in HeLa cells. Model/species: Human HeLa cervical cancer cells Tissue: Cell death and redox assays Exposure: Indicaxanthin 60 micromolar with cisplatin 10 micromolar; individual-agent controls Route: In vitro co-treatment Duration: 24 h Limits: Cell-culture chemosensitization is not clinical cancer efficacy. Redox-probe signals and protein changes do not prove direct target binding. Glutathione was assessed with CMFDA fluorescence; the result does not establish an isolated block of synthesis. Primary reference: The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis. (2020). https://pubmed.ncbi.nlm.nih.gov/32630700/ DOI: 10.3390/biom10070994 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

N-acetylcysteine 2 mM before indicaxanthin 60 micromolar plus cisplatin 10 micromolar

duration

NAC 1 h before the 24 h combination exposure

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human HeLa cervical cancer cells with NAC pretreatment

limitations

NAC blunted the combination response without restoring every outcome to baseline. This experiment is not a recommendation for or against NAC during chemotherapy.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human HeLa cervical cancer cells with NAC pretreatment

plain_language

N-acetylcysteine pretreatment reduced apoptosis caused by the indicaxanthin/cisplatin combination in HeLa cells.

primary_references

The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis. (2020). https://pubmed.ncbi.nlm.nih.gov/32630700/ DOI: 10.3390/biom10070994

route

In vitro pretreatment/co-treatment

tissue

Cell death and redox assays

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 327–336

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human HeLa cervical cancer cells with NAC pretreatment · source_derived_draft · unverified_draft

## indicaxanthin-nac-combination-antagonism N-acetylcysteine pretreatment reduced apoptosis caused by the indicaxanthin/cisplatin combination in HeLa cells. Model/species: Human HeLa cervical cancer cells with NAC pretreatment Tissue: Cell death and redox assays Exposure: N-acetylcysteine 2 mM before indicaxanthin 60 micromolar plus cisplatin 10 micromolar Route: In vitro pretreatment/co-treatment Duration: NAC 1 h before the 24 h combination exposure Limits: NAC blunted the combination response without restoring every outcome to baseline. This experiment is not a recommendation for or against NAC during chemotherapy. Primary reference: The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis. (2020). https://pubmed.ncbi.nlm.nih.gov/32630700/ DOI: 10.3390/biom10070994 Access: Primary open full text, relevant results/methods and PubMed metadata.

dose

Indicaxanthin 1-10 micromolar; cumene hydroperoxide challenge

duration

Not specified in accessed abstract

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human beta-thalassemia donor erythrocytes

limitations

Ex vivo redox protection is not demonstrated oral treatment of anemia; preservation is not proof of increased glutathione synthesis.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human beta-thalassemia donor erythrocytes

plain_language

Added indicaxanthin delayed glutathione depletion during oxidative challenge of beta-thalassemic red cells.

primary_references

Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16984002/ DOI: 10.1080/10715760600554228

route

Ex vivo addition

tissue

Red blood cells

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 41–50

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human beta-thalassemia donor erythrocytes · source_derived_draft · unverified_draft

## indicaxanthin-rbc-glutathione Added indicaxanthin delayed glutathione depletion during oxidative challenge of beta-thalassemic red cells. Model/species: Human beta-thalassemia donor erythrocytes Tissue: Red blood cells Exposure: Indicaxanthin 1-10 micromolar; cumene hydroperoxide challenge Route: Ex vivo addition Duration: Not specified in accessed abstract Limits: Ex vivo redox protection is not demonstrated oral treatment of anemia; preservation is not proof of increased glutathione synthesis. Primary reference: Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16984002/ DOI: 10.1080/10715760600554228 Access: Primary PubMed abstract.

dose

Betanin 2, 10 and 20 micromolar

duration

Not specified in accessed primary abstract

evidence_access

Primary PubMed abstract; detailed exposure for PMID 23931157 additionally checked in publisher results. No uninspected full text is claimed.

evidence_scope

literature_reviewed; source-derived curation, not universally established human effects

experimental_model

Human THLE-2 non-tumour liver and HepG2 hepatoma cell lines

limitations

Responses differed by cell line. Nuclear translocation is not proof of universal transcriptional activation; kinase association does not prove direct binding. Glutathione is the shared GST substrate; this study does not show betanin raises glutathione synthesis or reverses deficiency.

nutrient_topic

Betalains collection; each molecular form, species, exposure and preparation remains explicit. · Betalains

organism

Human THLE-2 non-tumour liver and HepG2 hepatoma cell lines

plain_language

Betanin increased GSTP transcript and protein abundance in THLE-2 cells.

primary_references

Betanin, a beetroot component, induces nuclear factor erythroid-2-related factor 2-mediated expression of detoxifying/antioxidant enzymes in human liver cell lines. (2013). https://pubmed.ncbi.nlm.nih.gov/23769299/ DOI: 10.1017/S0007114513001645

route

In vitro incubation

tissue

Liver-derived cells; cytosol and nucleus

Betalains: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 237–245

Original AI-assisted curation of twelve primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Human THLE-2 non-tumour liver and HepG2 hepatoma cell lines · source_derived_draft · unverified_draft

## betalains-gstp-expression Betanin increased GSTP transcript and protein abundance in THLE-2 cells. Model/species: Human THLE-2 non-tumour liver and HepG2 hepatoma cell lines Tissue: Liver-derived cells; cytosol and nucleus Exposure: Betanin 2, 10 and 20 micromolar Route: In vitro incubation Duration: Not specified in accessed primary abstract Limits: Responses differed by cell line. Nuclear translocation is not proof of universal transcriptional activation; kinase association does not prove direct binding. Glutathione is the shared GST substrate; this study does not show betanin raises glutathione synthesis or reverses deficiency. Primary reference: Betanin, a beetroot component, induces nuclear factor erythroid-2-related factor 2-mediated expression of detoxifying/antioxidant enzymes in human liver cell lines. (2013). https://pubmed.ncbi.nlm.nih.gov/23769299/ DOI: 10.1017/S0007114513001645

cross_nutrient

true

experimental_model

Purified human placental glutaredoxin and bovine liver PDI; additional porcine/bovine glutaredoxins

exposure

Purified PDI, DHA and GSH

limitations

Do not infer intact human endoplasmic-reticulum flux from this enzyme-capacity result.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Bos taurus

plain_language

A bovine protein-folding enzyme also recycled oxidized vitamin C in a purified assay.

primary_references

[wells1990] Mammalian thioltransferase (glutaredoxin) and protein disulfide isomerase have dehydroascorbate reductase activity. (1990). https://pubmed.ncbi.nlm.nih.gov/2394726/ DOI: 10.1016/s0021-9258(18)55401-6

tissue_or_cell_type

Liver enzyme preparation

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 364–375

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human placental glutaredoxin and bovine liver PDI; additional porcine/bovine glutaredoxins · source_derived_draft · unverified_draft

### vc-transport-bovine-pdi-dha Purified bovine liver protein disulfide isomerase catalyzed DHA reduction with GSH; apparent DHA Km was 1.0 mM. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: A bovine protein-folding enzyme also recycled oxidized vitamin C in a purified assay. organism: Bos taurus tissue_or_cell_type: Liver enzyme preparation experimental_model: Purified human placental glutaredoxin and bovine liver PDI; additional porcine/bovine glutaredoxins limitations: Do not infer intact human endoplasmic-reticulum flux from this enzyme-capacity result. exposure: Purified PDI, DHA and GSH cross_nutrient: true [wells1990] Mammalian thioltransferase (glutaredoxin) and protein disulfide isomerase have dehydroascorbate reductase activity. (1990). https://pubmed.ncbi.nlm.nih.gov/2394726/ DOI: 10.1016/s0021-9258(18)55401-6

cross_nutrient

true

experimental_model

Purified human placental glutaredoxin and bovine liver PDI; additional porcine/bovine glutaredoxins

exposure

Purified enzyme plus DHA and GSH

limitations

In vitro activity does not establish its share of total placental recycling.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Homo sapiens

plain_language

Glutaredoxin can use glutathione to restore reduced vitamin C.

primary_references

[wells1990] Mammalian thioltransferase (glutaredoxin) and protein disulfide isomerase have dehydroascorbate reductase activity. (1990). https://pubmed.ncbi.nlm.nih.gov/2394726/ DOI: 10.1016/s0021-9258(18)55401-6

tissue_or_cell_type

Placental enzyme preparation

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 351–362

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human placental glutaredoxin and bovine liver PDI; additional porcine/bovine glutaredoxins · source_derived_draft · unverified_draft

### vc-transport-human-glutaredoxin-dha Purified human placental glutaredoxin catalyzed GSH-dependent reduction of DHA to ascorbate. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutaredoxin can use glutathione to restore reduced vitamin C. organism: Homo sapiens tissue_or_cell_type: Placental enzyme preparation experimental_model: Purified human placental glutaredoxin and bovine liver PDI; additional porcine/bovine glutaredoxins limitations: In vitro activity does not establish its share of total placental recycling. exposure: Purified enzyme plus DHA and GSH cross_nutrient: true [wells1990] Mammalian thioltransferase (glutaredoxin) and protein disulfide isomerase have dehydroascorbate reductase activity. (1990). https://pubmed.ncbi.nlm.nih.gov/2394726/ DOI: 10.1016/s0021-9258(18)55401-6

cross_nutrient

true

experimental_model

Human volunteer erythrocytes ex vivo

exposure

Exogenous DHA concentration series

limitations

Assay loading capacity is not the normal circulating erythrocyte concentration.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Homo sapiens

plain_language

Red cells can recover reduced vitamin C from its oxidized form.

primary_references

[may2001] Mechanisms of ascorbic acid recycling in human erythrocytes. (2001). https://pubmed.ncbi.nlm.nih.gov/11687303/ DOI: 10.1016/s0304-4165(01)00188-x

tissue_or_cell_type

Erythrocytes

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 312–323

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human volunteer erythrocytes ex vivo · source_derived_draft · unverified_draft

### vc-transport-rbc-dha-recycling Human erythrocytes rapidly took up supplied DHA and accumulated ascorbate to concentrations up to 2 mM in the ex vivo assay. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Red cells can recover reduced vitamin C from its oxidized form. organism: Homo sapiens tissue_or_cell_type: Erythrocytes experimental_model: Human volunteer erythrocytes ex vivo limitations: Assay loading capacity is not the normal circulating erythrocyte concentration. exposure: Exogenous DHA concentration series cross_nutrient: true [may2001] Mechanisms of ascorbic acid recycling in human erythrocytes. (2001). https://pubmed.ncbi.nlm.nih.gov/11687303/ DOI: 10.1016/s0304-4165(01)00188-x

cross_nutrient

true

experimental_model

Human volunteer erythrocytes ex vivo

exposure

DHA challenge with or without 5 mM glucose

limitations

Metabolic support and transporter competition are different processes; this does not imply dietary sugar supplementation is needed.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Homo sapiens

plain_language

Glucose metabolism helped sustain the reducing resources used to recycle vitamin C.

primary_references

[may2001] Mechanisms of ascorbic acid recycling in human erythrocytes. (2001). https://pubmed.ncbi.nlm.nih.gov/11687303/ DOI: 10.1016/s0304-4165(01)00188-x

tissue_or_cell_type

Erythrocytes

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 325–336

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human volunteer erythrocytes ex vivo · source_derived_draft · unverified_draft

### vc-transport-rbc-glucose-support During DHA reduction by human erythrocytes, 5 mM D-glucose maintained GSH and NADH concentrations whereas NADPH still declined; without glucose all three fell. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glucose metabolism helped sustain the reducing resources used to recycle vitamin C. organism: Homo sapiens tissue_or_cell_type: Erythrocytes experimental_model: Human volunteer erythrocytes ex vivo limitations: Metabolic support and transporter competition are different processes; this does not imply dietary sugar supplementation is needed. exposure: DHA challenge with or without 5 mM glucose cross_nutrient: true [may2001] Mechanisms of ascorbic acid recycling in human erythrocytes. (2001). https://pubmed.ncbi.nlm.nih.gov/11687303/ DOI: 10.1016/s0304-4165(01)00188-x

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

true

experimental_model

Human volunteer erythrocytes ex vivo

exposure

Up to 1 mM diethyl maleate ex vivo

limitations

Chemical depletion, not dietary deficiency; combined uptake/reduction readout does not isolate membrane transport.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Homo sapiens

plain_language

Depleting glutathione impaired the red cells’ vitamin C recycling capacity.

primary_references

[may2001] Mechanisms of ascorbic acid recycling in human erythrocytes. (2001). https://pubmed.ncbi.nlm.nih.gov/11687303/ DOI: 10.1016/s0304-4165(01)00188-x

tissue_or_cell_type

Erythrocytes

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 338–349

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human volunteer erythrocytes ex vivo · source_derived_draft · unverified_draft

### vc-transport-rbc-gsh-depletion Diethyl maleate depletion of erythrocyte GSH by 75–90% reduced the combined uptake and conversion of DHA to ascorbate in human cells. Condition category: machinery_impairment nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Depleting glutathione impaired the red cells’ vitamin C recycling capacity. organism: Homo sapiens tissue_or_cell_type: Erythrocytes experimental_model: Human volunteer erythrocytes ex vivo limitations: Chemical depletion, not dietary deficiency; combined uptake/reduction readout does not isolate membrane transport. exposure: Up to 1 mM diethyl maleate ex vivo cross_nutrient: true [may2001] Mechanisms of ascorbic acid recycling in human erythrocytes. (2001). https://pubmed.ncbi.nlm.nih.gov/11687303/ DOI: 10.1016/s0304-4165(01)00188-x

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

true

experimental_model

Purified rat liver thioredoxin reductase/thioredoxin and selenium-deficient rat liver

exposure

Dietary selenium deficiency

limitations

Several selenoenzymes were affected, including glutathione peroxidase; cannot attribute the entire ascorbate decrease solely to thioredoxin reductase.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Rattus norvegicus

plain_language

Selenium shortage reduced a vitamin C recycling pathway and liver vitamin C in rats.

primary_references

[may1997] Reduction of dehydroascorbate to ascorbate by the selenoenzyme thioredoxin reductase. (1997). https://pubmed.ncbi.nlm.nih.gov/9278416/ DOI: 10.1074/jbc.272.36.22607

tissue_or_cell_type

Liver

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 403–414

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified rat liver thioredoxin reductase/thioredoxin and selenium-deficient rat liver · source_derived_draft · unverified_draft

### vc-transport-selenium-liver-ascorbate Selenium-deficient rats had 33% less liver ascorbate together with an 88% fall in thioredoxin-reductase activity; liver GSH content was unchanged. Condition category: nutrient_deficiency nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Selenium shortage reduced a vitamin C recycling pathway and liver vitamin C in rats. organism: Rattus norvegicus tissue_or_cell_type: Liver experimental_model: Purified rat liver thioredoxin reductase/thioredoxin and selenium-deficient rat liver limitations: Several selenoenzymes were affected, including glutathione peroxidase; cannot attribute the entire ascorbate decrease solely to thioredoxin reductase. exposure: Dietary selenium deficiency cross_nutrient: true [may1997] Reduction of dehydroascorbate to ascorbate by the selenoenzyme thioredoxin reductase. (1997). https://pubmed.ncbi.nlm.nih.gov/9278416/ DOI: 10.1074/jbc.272.36.22607

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"}

experimental_model

Cell challenge with siRNA and pathway inhibitors

exposure

Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors

limitations

Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms.

nutrient_topic

Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin

organism

Human ARPE-19 cell line

plain_language

Pigment supply did not overcome the blocked glutathione response.

primary_references

[zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190

tissue_or_cell_type

Retinal pigment epithelial model

trigger_kind

machinery_impairment Imported condition classification; unverified.

Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 457–468

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell challenge with siRNA and pathway inhibitors · source_derived_draft · unverified_draft

### zeaxanthin-bso-failure BSO abolished zeaxanthin-associated protection of cell viability and mitochondrial membrane potential. Condition category: machinery_impairment nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Pigment supply did not overcome the blocked glutathione response. organism: Human ARPE-19 cell line tissue_or_cell_type: Retinal pigment epithelial model experimental_model: Cell challenge with siRNA and pathway inhibitors limitations: Pharmacological cell exposures are not dietary concentrations. PI3K/Akt inhibitor evidence is not direct zeaxanthin binding to a kinase. Liposome GSTP1 protection and this cellular GSH-dependent response are different mechanisms. exposure: Zeaxanthin commonly 10 micromolar for 24 h; 300 micromolar t-BHP challenge for 6 h; study-specific inhibitors evidence_span: {"source_cache": "artifacts/zeaxanthin-research/24810054.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f185c805dd5d825445cb40e547b794fbc595388aff6e2d29ac81c2eab8b8348", "start_char": 5813, "end_char": 15716, "text_sha256": "89e6abf1967c10b359cb62d935d5b839cf53acf42576d9db3d463bff9f474e38"} [zeaxanthin-p24810054] Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. (2014). https://pubmed.ncbi.nlm.nih.gov/24810054/ DOI: 10.1038/cddis.2014.190

evidence_span

{"source_cache": "artifacts/zeaxanthin-research/15949677.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4ed175c0b5cf937df5a37c94739b40d713261c3a99e2bebc02b3b6a37ea3f194", "start_char": 0, "end_char": 1404, "text_sha256": "4ed175c0b5cf937df5a37c94739b40d713261c3a99e2bebc02b3b6a37ea3f194"}

experimental_model

Lipid-peroxyl radical challenge in liposomes

exposure

AAPH or AMVN challenge; dietary and meso zeaxanthin

limitations

Protein-associated antioxidant synergy is demonstrated in this assay, not a clinical supplement combination.

nutrient_topic

Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin

organism

Cell-free system with human GSTP1

plain_language

This binding-related effect persisted without glutathione.

primary_references

[zeaxanthin-p15949677] Synergistic effects of zeaxanthin and its binding protein in the prevention of lipid membrane oxidation. (2005). https://pubmed.ncbi.nlm.nih.gov/15949677/ DOI: 10.1016/j.bbadis.2005.02.002

tissue_or_cell_type

Egg-yolk phosphatidylcholine liposomes

Zeaxanthin: metabolism, signaling and nutrient connections (2026-09-17) · lines 288–299

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lipid-peroxyl radical challenge in liposomes · source_derived_draft · unverified_draft

### zeaxanthin-gsh-independent The GSTP1–zeaxanthin protective effect did not require glutathione in this liposome experiment. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This binding-related effect persisted without glutathione. organism: Cell-free system with human GSTP1 tissue_or_cell_type: Egg-yolk phosphatidylcholine liposomes experimental_model: Lipid-peroxyl radical challenge in liposomes limitations: Protein-associated antioxidant synergy is demonstrated in this assay, not a clinical supplement combination. exposure: AAPH or AMVN challenge; dietary and meso zeaxanthin evidence_span: {"source_cache": "artifacts/zeaxanthin-research/15949677.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4ed175c0b5cf937df5a37c94739b40d713261c3a99e2bebc02b3b6a37ea3f194", "start_char": 0, "end_char": 1404, "text_sha256": "4ed175c0b5cf937df5a37c94739b40d713261c3a99e2bebc02b3b6a37ea3f194"} [zeaxanthin-p15949677] Synergistic effects of zeaxanthin and its binding protein in the prevention of lipid membrane oxidation. (2005). https://pubmed.ncbi.nlm.nih.gov/15949677/ DOI: 10.1016/j.bbadis.2005.02.002

acting_entity

s-allylcysteine

dose

SAC 25 mg/kg; cisplatin dose not retrieved

duration

Single SAC dose for signaling arm; timing not retrieved

evidence_access

Primary abstract

experimental_comparison

SAC with cisplatin versus cisplatin injury controls

experimental_model

Cisplatin-challenged renal cortex and isolated proximal/distal tubules

interpretation_status

Source-derived research curation; not independent primary verification

limitations

Isoforms were not resolved; activity preservation does not demonstrate selenium or riboflavin repletion.

nutrient_topic

S-allylcysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · S-allyl-L-cysteine / SAC

organism

Rattus norvegicus

plain_language

Several antioxidant activities were retained during injury.

primary_references

[24779924] S-allylcysteine prevents cisplatin-induced nephrotoxicity and oxidative stress. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24779924/ · DOI 10.1111/jphp.12263

route

Administration route not specified in accessed abstract

tissue_or_cell_type

Cisplatin-challenged renal cortex and isolated proximal/distal tubules

S-allylcysteine: sulfur signaling, redox responses and cross-nutrient mechanisms (2026-09-20) · lines 356–363

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cisplatin-challenged renal cortex and isolated proximal/distal tubules · source_derived_draft · unverified_draft

## s-allylcysteine-cisplatin-antioxidant-enzymes Several antioxidant activities were retained during injury. SAC attenuated cisplatin-associated losses of catalase, GPx and glutathione reductase activities in proximal and distal tubules. Model: Cisplatin-challenged renal cortex and isolated proximal/distal tubules Limitations: Isoforms were not resolved; activity preservation does not demonstrate selenium or riboflavin repletion. Evidence access: Primary abstract [24779924] S-allylcysteine prevents cisplatin-induced nephrotoxicity and oxidative stress. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24779924/ · DOI 10.1111/jphp.12263 Structured context: {"organism": "Rattus norvegicus", "tissue_or_cell_type": "Cisplatin-challenged renal cortex and isolated proximal/distal tubules", "dose": "SAC 25 mg/kg; cisplatin dose not retrieved", "duration": "Single SAC dose for signaling arm; timing not retrieved", "route": "Administration route not specified in accessed abstract", "experimental_comparison": "SAC with cisplatin versus cisplatin injury controls", "acting_entity": "s-allylcysteine", "interpretation_status": "Source-derived research curation; not independent primary verification"}

acting_entity

s-allylcysteine

dose

Not specified in accessed abstract

duration

Not specified in accessed abstract

evidence_access

Primary abstract

experimental_comparison

SAC with PhIP challenge and corresponding cell controls

experimental_model

Normal human colonic mucosal epithelial cells exposed to PhIP

interpretation_status

Source-derived research curation; not independent primary verification

limitations

The abstract describes the ratio ambiguously as GSH to GSH/GSSG; exact numerator/denominator require full-text clarification. No cysteine donation is inferred.

nutrient_topic

S-allylcysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · S-allyl-L-cysteine / SAC

organism

Homo sapiens

plain_language

The glutathione readout is retained without inventing a precursor flux.

primary_references

[35753083] S-Allylcysteine Potently Protects against PhIP-Induced DNA Damage via Nrf2/AhR Signaling Pathway Modulation in Normal Human Colonic Mucosal Epithelial Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35753083/ · DOI 10.1002/mnfr.202101141

route

Cell culture

tissue_or_cell_type

Normal human colonic mucosal epithelial cells exposed to PhIP

S-allylcysteine: sulfur signaling, redox responses and cross-nutrient mechanisms (2026-09-20) · lines 176–183

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Normal human colonic mucosal epithelial cells exposed to PhIP · source_derived_draft · unverified_draft

## s-allylcysteine-colon-redox The glutathione readout is retained without inventing a precursor flux. The study reported an improved glutathione-related redox ratio with SAC during PhIP exposure. Model: Normal human colonic mucosal epithelial cells exposed to PhIP Limitations: The abstract describes the ratio ambiguously as GSH to GSH/GSSG; exact numerator/denominator require full-text clarification. No cysteine donation is inferred. Evidence access: Primary abstract [35753083] S-Allylcysteine Potently Protects against PhIP-Induced DNA Damage via Nrf2/AhR Signaling Pathway Modulation in Normal Human Colonic Mucosal Epithelial Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35753083/ · DOI 10.1002/mnfr.202101141 Structured context: {"organism": "Homo sapiens", "tissue_or_cell_type": "Normal human colonic mucosal epithelial cells exposed to PhIP", "dose": "Not specified in accessed abstract", "duration": "Not specified in accessed abstract", "route": "Cell culture", "experimental_comparison": "SAC with PhIP challenge and corresponding cell controls", "acting_entity": "s-allylcysteine", "interpretation_status": "Source-derived research curation; not independent primary verification"}

acting_entity

s-allylcysteine

availability_state

nutrient_deficiency Imported condition classification; unverified.

dose

SAC 1 g/L drinking water

duration

Seven weeks

evidence_access

Primary abstract

experimental_comparison

SAC or S-ethylcysteine separately with deficient diet versus diet controls

experimental_model

Methionine/choline-deficient diet; liver and serum measurements

interpretation_status

Source-derived research curation; not independent primary verification

limitations

Does not establish replacement of methionine or choline, or direct donation of cysteine to GSH.

nutrient_topic

S-allylcysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · S-allyl-L-cysteine / SAC

organism

Mus musculus

plain_language

A nutrient-deficiency model connects SAC to glutathione status.

primary_references

[18786595] Alleviative effects of s-allyl cysteine and s-ethyl cysteine on MCD diet-induced hepatotoxicity in mice. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18786595/ · DOI 10.1016/j.fct.2008.08.010

route

Oral drinking water

tissue_or_cell_type

Methionine/choline-deficient diet; liver and serum measurements

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

S-allylcysteine: sulfur signaling, redox responses and cross-nutrient mechanisms (2026-09-20) · lines 365–372

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Methionine/choline-deficient diet; liver and serum measurements · source_derived_draft · unverified_draft

## s-allylcysteine-mcd-glutathione A nutrient-deficiency model connects SAC to glutathione status. SAC in drinking water increased serum and hepatic GSH during methionine/choline-deficient feeding. Model: Methionine/choline-deficient diet; liver and serum measurements Limitations: Does not establish replacement of methionine or choline, or direct donation of cysteine to GSH. Evidence access: Primary abstract [18786595] Alleviative effects of s-allyl cysteine and s-ethyl cysteine on MCD diet-induced hepatotoxicity in mice. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18786595/ · DOI 10.1016/j.fct.2008.08.010 Structured context: {"organism": "Mus musculus", "tissue_or_cell_type": "Methionine/choline-deficient diet; liver and serum measurements", "dose": "SAC 1 g/L drinking water", "duration": "Seven weeks", "route": "Oral drinking water", "experimental_comparison": "SAC or S-ethylcysteine separately with deficient diet versus diet controls", "acting_entity": "s-allylcysteine", "interpretation_status": "Source-derived research curation; not independent primary verification"}

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/glutathione-research/34707288.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5", "start_char": 0, "end_char": 1450, "text_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5"}

experimental_model

Organelle metabolomics, genetics and targeted synthesis rescue

exposure

SLC25A39 loss, A39/A40 double loss and targeted GshF

limitations

Mitochondrial versus total-cell pools differ; engineered synthesis rescue is not oral supplementation.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Mammalian cells; separate mouse erythropoiesis experiments

plain_language

Glutathione availability connects to cofactor construction as well as oxidation control.

primary_references

[glutathione-p34707288] SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. (2021). https://pubmed.ncbi.nlm.nih.gov/34707288/ DOI: 10.1038/s41586-021-04025-w

tissue_or_cell_type

Mitochondria

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 489–500

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Organelle metabolomics, genetics and targeted synthesis rescue · source_derived_draft · unverified_draft

### glutathione-a39-a40-fes Combined A39/A40 loss impaired activity and stability of iron-sulfur proteins. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione availability connects to cofactor construction as well as oxidation control. organism: Mammalian cells; separate mouse erythropoiesis experiments tissue_or_cell_type: Mitochondria experimental_model: Organelle metabolomics, genetics and targeted synthesis rescue limitations: Mitochondrial versus total-cell pools differ; engineered synthesis rescue is not oral supplementation. exposure: SLC25A39 loss, A39/A40 double loss and targeted GshF evidence_span: {"source_cache": "artifacts/glutathione-research/34707288.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5", "start_char": 0, "end_char": 1450, "text_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5"} [glutathione-p34707288] SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. (2021). https://pubmed.ncbi.nlm.nih.gov/34707288/ DOI: 10.1038/s41586-021-04025-w

evidence_span

{"source_cache": "artifacts/glutathione-research/34707288.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5", "start_char": 0, "end_char": 1450, "text_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5"}

experimental_model

Organelle metabolomics, genetics and targeted synthesis rescue

exposure

SLC25A39 loss, A39/A40 double loss and targeted GshF

limitations

Mitochondrial versus total-cell pools differ; engineered synthesis rescue is not oral supplementation.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Mammalian cells; separate mouse erythropoiesis experiments

plain_language

Making glutathione is not enough if it cannot enter this compartment.

primary_references

[glutathione-p34707288] SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. (2021). https://pubmed.ncbi.nlm.nih.gov/34707288/ DOI: 10.1038/s41586-021-04025-w

tissue_or_cell_type

Mitochondria

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 450–461

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Organelle metabolomics, genetics and targeted synthesis rescue · source_derived_draft · unverified_draft

### glutathione-a39-import SLC25A39 loss reduced mitochondrial GSH import. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Making glutathione is not enough if it cannot enter this compartment. organism: Mammalian cells; separate mouse erythropoiesis experiments tissue_or_cell_type: Mitochondria experimental_model: Organelle metabolomics, genetics and targeted synthesis rescue limitations: Mitochondrial versus total-cell pools differ; engineered synthesis rescue is not oral supplementation. exposure: SLC25A39 loss, A39/A40 double loss and targeted GshF evidence_span: {"source_cache": "artifacts/glutathione-research/34707288.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5", "start_char": 0, "end_char": 1450, "text_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5"} [glutathione-p34707288] SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. (2021). https://pubmed.ncbi.nlm.nih.gov/34707288/ DOI: 10.1038/s41586-021-04025-w

evidence_span

{"source_cache": "artifacts/glutathione-research/35513392.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "000d49d8bad7e173d95c214f6cb2bf2ea84b9e4af231687687d1aa703cdeaff7", "start_char": 0, "end_char": 1457, "text_sha256": "000d49d8bad7e173d95c214f6cb2bf2ea84b9e4af231687687d1aa703cdeaff7"}

experimental_model

Paired CRISPR screen and mitochondrial transport assays

exposure

2016 single/pair perturbations across four metabolic states

limitations

Genetic buffering depends on metabolic conditions; it is not evidence that iron supplementation corrects low GSH.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human experimental cells

plain_language

A second study supported the carrier assignment.

primary_references

[glutathione-p35513392] Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS. (2022). https://pubmed.ncbi.nlm.nih.gov/35513392/ DOI: 10.1038/s41467-022-30126-9

tissue_or_cell_type

Mitochondrial transport and respiration

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 515–526

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Paired CRISPR screen and mitochondrial transport assays · source_derived_draft · unverified_draft

### glutathione-a39-independent An independent CRISPR/transport study identified SLC25A39 as critical for mitochondrial GSH import. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second study supported the carrier assignment. organism: Human experimental cells tissue_or_cell_type: Mitochondrial transport and respiration experimental_model: Paired CRISPR screen and mitochondrial transport assays limitations: Genetic buffering depends on metabolic conditions; it is not evidence that iron supplementation corrects low GSH. exposure: 2016 single/pair perturbations across four metabolic states evidence_span: {"source_cache": "artifacts/glutathione-research/35513392.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "000d49d8bad7e173d95c214f6cb2bf2ea84b9e4af231687687d1aa703cdeaff7", "start_char": 0, "end_char": 1457, "text_sha256": "000d49d8bad7e173d95c214f6cb2bf2ea84b9e4af231687687d1aa703cdeaff7"} [glutathione-p35513392] Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS. (2022). https://pubmed.ncbi.nlm.nih.gov/35513392/ DOI: 10.1038/s41467-022-30126-9

evidence_span

{"source_cache": "artifacts/glutathione-research/25931127.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1", "start_char": 0, "end_char": 1504, "text_sha256": "a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1"}

experimental_model

Human promoter reporters, binding assays and overexpression

exposure

ER stress, ATF4 and CHAC1 expression

limitations

Cell experiments; CHAC1 induction is not a dietary GSH-deficiency diagnosis.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

Low glutathione can reflect increased breakdown, not just poor supply.

primary_references

[glutathione-p25931127] Human CHAC1 Protein Degrades Glutathione, and mRNA Induction Is Regulated by the Transcription Factors ATF4 and ATF3 and a Bipartite ATF/CRE Regulatory Element. (2015). https://pubmed.ncbi.nlm.nih.gov/25931127/ DOI: 10.1074/jbc.m114.635144

tissue_or_cell_type

HEK293 and U2OS cells

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 580–591

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human promoter reporters, binding assays and overexpression · source_derived_draft · unverified_draft

### glutathione-chac1-gsh CHAC1 overexpression depleted GSH in HEK293 cells; a catalytic mutation alleviated that depletion. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low glutathione can reflect increased breakdown, not just poor supply. organism: Human tissue_or_cell_type: HEK293 and U2OS cells experimental_model: Human promoter reporters, binding assays and overexpression limitations: Cell experiments; CHAC1 induction is not a dietary GSH-deficiency diagnosis. exposure: ER stress, ATF4 and CHAC1 expression evidence_span: {"source_cache": "artifacts/glutathione-research/25931127.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1", "start_char": 0, "end_char": 1504, "text_sha256": "a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1"} [glutathione-p25931127] Human CHAC1 Protein Degrades Glutathione, and mRNA Induction Is Regulated by the Transcription Factors ATF4 and ATF3 and a Bipartite ATF/CRE Regulatory Element. (2015). https://pubmed.ncbi.nlm.nih.gov/25931127/ DOI: 10.1074/jbc.m114.635144

evidence_span

{"source_cache": "artifacts/glutathione-research/8099811.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "53a6b1a1855863d8fe1d0be289055e7cd6ca39b33e936e82dfed2d7d084c9d5b", "start_char": 0, "end_char": 984, "text_sha256": "53a6b1a1855863d8fe1d0be289055e7cd6ca39b33e936e82dfed2d7d084c9d5b"}

experimental_model

Human GGT transfection in mouse fibroblasts

exposure

Cysteine-free medium supplemented with extracellular GSH

limitations

Precursor salvage after extracellular cleavage; not proof of intact oral GSH entry into every tissue.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human GGT; NIH/3T3 host

plain_language

Breaking down glutathione outside a cell can supply building blocks inside.

primary_references

[glutathione-p8099811] Extracellular glutathione is a source of cysteine for cells that express gamma-glutamyl transpeptidase. (1993). https://pubmed.ncbi.nlm.nih.gov/8099811/ DOI: 10.1021/bi00075a026

tissue_or_cell_type

Cell surface and intracellular pools

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 632–643

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human GGT transfection in mouse fibroblasts · source_derived_draft · unverified_draft

### glutathione-ggt-cysteine Human-GGT-expressing fibroblasts used extracellular GSH as a cysteine source in cysteine-free medium. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Breaking down glutathione outside a cell can supply building blocks inside. organism: Human GGT; NIH/3T3 host tissue_or_cell_type: Cell surface and intracellular pools experimental_model: Human GGT transfection in mouse fibroblasts limitations: Precursor salvage after extracellular cleavage; not proof of intact oral GSH entry into every tissue. exposure: Cysteine-free medium supplemented with extracellular GSH evidence_span: {"source_cache": "artifacts/glutathione-research/8099811.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "53a6b1a1855863d8fe1d0be289055e7cd6ca39b33e936e82dfed2d7d084c9d5b", "start_char": 0, "end_char": 984, "text_sha256": "53a6b1a1855863d8fe1d0be289055e7cd6ca39b33e936e82dfed2d7d084c9d5b"} [glutathione-p8099811] Extracellular glutathione is a source of cysteine for cells that express gamma-glutamyl transpeptidase. (1993). https://pubmed.ncbi.nlm.nih.gov/8099811/ DOI: 10.1021/bi00075a026

evidence_span

{"source_cache": "artifacts/glutathione-research/9218781.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e00867a8f693a2a0e6506a87d162a52ce4aa75ac846c7b0495dcf6ad7c9330e1", "start_char": 0, "end_char": 1251, "text_sha256": "e00867a8f693a2a0e6506a87d162a52ce4aa75ac846c7b0495dcf6ad7c9330e1"}

experimental_model

Human GLO1 crystal structure

exposure

S-benzyl-GSH complex

limitations

The essential zinc site is biochemical evidence; neither zinc nor GSH supplementation was tested.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

Glutathione also participates in handling a reactive carbonyl compound.

primary_references

[glutathione-p9218781] Crystal structure of human glyoxalase I--evidence for gene duplication and 3D domain swapping. (1997). https://pubmed.ncbi.nlm.nih.gov/9218781/ DOI: 10.1093/emboj/16.12.3386

tissue_or_cell_type

Purified dimeric enzyme

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 879–890

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human GLO1 crystal structure · source_derived_draft · unverified_draft

### glutathione-glo1-methylglyoxal Human GLO1 catalyzes glutathione-dependent methylglyoxal inactivation. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione also participates in handling a reactive carbonyl compound. organism: Human tissue_or_cell_type: Purified dimeric enzyme experimental_model: Human GLO1 crystal structure limitations: The essential zinc site is biochemical evidence; neither zinc nor GSH supplementation was tested. exposure: S-benzyl-GSH complex evidence_span: {"source_cache": "artifacts/glutathione-research/9218781.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e00867a8f693a2a0e6506a87d162a52ce4aa75ac846c7b0495dcf6ad7c9330e1", "start_char": 0, "end_char": 1251, "text_sha256": "e00867a8f693a2a0e6506a87d162a52ce4aa75ac846c7b0495dcf6ad7c9330e1"} [glutathione-p9218781] Crystal structure of human glyoxalase I--evidence for gene duplication and 3D domain swapping. (1997). https://pubmed.ncbi.nlm.nih.gov/9218781/ DOI: 10.1093/emboj/16.12.3386

evidence_span

{"source_cache": "artifacts/glutathione-research/6863314.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fc40fe8d31ed36ad75af255cf31121d46ab8905d456f4ff9d94cc857e6b0e00d", "start_char": 0, "end_char": 2097, "text_sha256": "fc40fe8d31ed36ad75af255cf31121d46ab8905d456f4ff9d94cc857e6b0e00d"}

experimental_model

Forward/reverse enzyme kinetics

exposure

Lactoyl-GSH and thiol-trapping experiments

limitations

Artificial trapping reveals reversibility; it does not reverse the usual physiological net flux.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human erythrocyte enzyme; separate yeast comparison

plain_language

The first enzyme supplies the substrate processed by glyoxalase II.

primary_references

[glutathione-p6863314] Reversal of the reaction catalyzed by glyoxalase I. Calculation of the equilibrium constant for the enzymatic reaction. (1983). https://pubmed.ncbi.nlm.nih.gov/6863314/ DOI: 10.1016/s0021-9258(18)32137-9

tissue_or_cell_type

Purified glyoxalase I

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 918–929

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Forward/reverse enzyme kinetics · source_derived_draft · unverified_draft

### glutathione-glo1-product Human erythrocyte GLO1 forms S-D-lactoylglutathione through the methylglyoxal/GSH hemithioacetal intermediate. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The first enzyme supplies the substrate processed by glyoxalase II. organism: Human erythrocyte enzyme; separate yeast comparison tissue_or_cell_type: Purified glyoxalase I experimental_model: Forward/reverse enzyme kinetics limitations: Artificial trapping reveals reversibility; it does not reverse the usual physiological net flux. exposure: Lactoyl-GSH and thiol-trapping experiments evidence_span: {"source_cache": "artifacts/glutathione-research/6863314.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fc40fe8d31ed36ad75af255cf31121d46ab8905d456f4ff9d94cc857e6b0e00d", "start_char": 0, "end_char": 2097, "text_sha256": "fc40fe8d31ed36ad75af255cf31121d46ab8905d456f4ff9d94cc857e6b0e00d"} [glutathione-p6863314] Reversal of the reaction catalyzed by glyoxalase I. Calculation of the equilibrium constant for the enzymatic reaction. (1983). https://pubmed.ncbi.nlm.nih.gov/6863314/ DOI: 10.1016/s0021-9258(18)32137-9

evidence_span

{"source_cache": "artifacts/glutathione-research/10508780.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2a3bc96920fd7c09bc46bfbdd6ade9698bb3dd421e0867023dec7679628d04eb", "start_char": 0, "end_char": 1432, "text_sha256": "2a3bc96920fd7c09bc46bfbdd6ade9698bb3dd421e0867023dec7679628d04eb"}

experimental_model

Crystal structures of free and ligand-bound GLO2

exposure

Thioester hydrolysis and substrate-analogue structure

limitations

The structure contained a binuclear zinc site; metal occupancy in this preparation is not a universal in-vivo metal assignment.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

This clearance route regenerates glutathione instead of permanently consuming it.

primary_references

[glutathione-p10508780] Crystal structure of human glyoxalase II and its complex with a glutathione thiolester substrate analogue. (1999). https://pubmed.ncbi.nlm.nih.gov/10508780/ DOI: 10.1016/s0969-2126(99)80174-9

tissue_or_cell_type

Purified glyoxalase II

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 905–916

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structures of free and ligand-bound GLO2 · source_derived_draft · unverified_draft

### glutathione-glo2-recycles Human glyoxalase II hydrolyzes S-D-lactoylglutathione to GSH and D-lactate. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: This clearance route regenerates glutathione instead of permanently consuming it. organism: Human tissue_or_cell_type: Purified glyoxalase II experimental_model: Crystal structures of free and ligand-bound GLO2 limitations: The structure contained a binuclear zinc site; metal occupancy in this preparation is not a universal in-vivo metal assignment. exposure: Thioester hydrolysis and substrate-analogue structure evidence_span: {"source_cache": "artifacts/glutathione-research/10508780.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2a3bc96920fd7c09bc46bfbdd6ade9698bb3dd421e0867023dec7679628d04eb", "start_char": 0, "end_char": 1432, "text_sha256": "2a3bc96920fd7c09bc46bfbdd6ade9698bb3dd421e0867023dec7679628d04eb"} [glutathione-p10508780] Crystal structure of human glyoxalase II and its complex with a glutathione thiolester substrate analogue. (1999). https://pubmed.ncbi.nlm.nih.gov/10508780/ DOI: 10.1016/s0969-2126(99)80174-9

evidence_span

{"source_cache": "artifacts/glutathione-research/14676218.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a7399b7d035bd3815c30362449b7986dea08873c824e05506d7db627a71daa84", "start_char": 0, "end_char": 1398, "text_sha256": "a7399b7d035bd3815c30362449b7986dea08873c824e05506d7db627a71daa84"}

experimental_model

Purified human glutaredoxin kinetics and mutants

exposure

GSH or NADPH/thioredoxin-reductase donor systems

limitations

Biochemical electron-donor alternatives; no claim that all cellular GLRX2 uses one route.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human GLRX1/GLRX2

plain_language

Glutathione attached to a protein can be removed enzymatically.

primary_references

[glutathione-p14676218] Human mitochondrial glutaredoxin reduces S-glutathionylated proteins with high affinity accepting electrons from either glutathione or thioredoxin reductase. (2004). https://pubmed.ncbi.nlm.nih.gov/14676218/ DOI: 10.1074/jbc.m312719200

tissue_or_cell_type

Glutathionylated substrates

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 814–825

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human glutaredoxin kinetics and mutants · source_derived_draft · unverified_draft

### glutathione-glrx2-deglutathionylation GLRX2 reduced glutathionylated substrates with lower rate but higher affinity than GLRX1, giving similar catalytic efficiency. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione attached to a protein can be removed enzymatically. organism: Human GLRX1/GLRX2 tissue_or_cell_type: Glutathionylated substrates experimental_model: Purified human glutaredoxin kinetics and mutants limitations: Biochemical electron-donor alternatives; no claim that all cellular GLRX2 uses one route. exposure: GSH or NADPH/thioredoxin-reductase donor systems evidence_span: {"source_cache": "artifacts/glutathione-research/14676218.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a7399b7d035bd3815c30362449b7986dea08873c824e05506d7db627a71daa84", "start_char": 0, "end_char": 1398, "text_sha256": "a7399b7d035bd3815c30362449b7986dea08873c824e05506d7db627a71daa84"} [glutathione-p14676218] Human mitochondrial glutaredoxin reduces S-glutathionylated proteins with high affinity accepting electrons from either glutathione or thioredoxin reductase. (2004). https://pubmed.ncbi.nlm.nih.gov/14676218/ DOI: 10.1074/jbc.m312719200

evidence_span

{"source_cache": "artifacts/glutathione-research/10369661.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccdd02e451ba6a6d432012c382911ff7fac556e99f9e8d60ce9f3dc94baf9941", "start_char": 0, "end_char": 1327, "text_sha256": "ccdd02e451ba6a6d432012c382911ff7fac556e99f9e8d60ce9f3dc94baf9941"}

experimental_model

Crystal structure and disease-variant mapping

exposure

ADP/GSH/sulfate-bound structure

limitations

Two Mg ions observed; structure is not a dietary-magnesium depletion experiment. The main synthesis reaction is reused from its existing claim.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human enzyme

plain_language

The synthesis enzyme has a metal-containing nucleotide-binding environment.

primary_references

[glutathione-p10369661] Molecular basis of glutathione synthetase deficiency and a rare gene permutation event. (1999). https://pubmed.ncbi.nlm.nih.gov/10369661/ DOI: 10.1093/emboj/18.12.3204

tissue_or_cell_type

Purified GSS

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 333–344

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structure and disease-variant mapping · source_derived_draft · unverified_draft

### glutathione-gss-magnesium Human GSS crystallized with two magnesium ions, ADP, glutathione and sulfate. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The synthesis enzyme has a metal-containing nucleotide-binding environment. organism: Human enzyme tissue_or_cell_type: Purified GSS experimental_model: Crystal structure and disease-variant mapping limitations: Two Mg ions observed; structure is not a dietary-magnesium depletion experiment. The main synthesis reaction is reused from its existing claim. exposure: ADP/GSH/sulfate-bound structure evidence_span: {"source_cache": "artifacts/glutathione-research/10369661.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccdd02e451ba6a6d432012c382911ff7fac556e99f9e8d60ce9f3dc94baf9941", "start_char": 0, "end_char": 1327, "text_sha256": "ccdd02e451ba6a6d432012c382911ff7fac556e99f9e8d60ce9f3dc94baf9941"} [glutathione-p10369661] Molecular basis of glutathione synthetase deficiency and a rare gene permutation event. (1999). https://pubmed.ncbi.nlm.nih.gov/10369661/ DOI: 10.1093/emboj/18.12.3204

evidence_span

{"source_cache": "artifacts/glutathione-research/20980252.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5eacc338c23e1f1be126ba80eebc8ac0ce7ea8735f22a5583dcebd7ef44eded4", "start_char": 0, "end_char": 1776, "text_sha256": "5eacc338c23e1f1be126ba80eebc8ac0ce7ea8735f22a5583dcebd7ef44eded4"}

experimental_model

LTC4S mutagenesis, spectroscopy and crystallography

exposure

Arg104 and Arg31 substitutions

limitations

GSH participates in inflammatory mediator synthesis; biochemical use does not imply that GSH supplements cause asthma.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

Glutathione is also a building block for a signaling molecule.

primary_references

[glutathione-p20980252] Arginine 104 is a key catalytic residue in leukotriene C4 synthase. (2010). https://pubmed.ncbi.nlm.nih.gov/20980252/ DOI: 10.1074/jbc.m110.105940

tissue_or_cell_type

Purified membrane enzyme

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 931–942

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · LTC4S mutagenesis, spectroscopy and crystallography · source_derived_draft · unverified_draft

### glutathione-ltc4s-product Human LTC4S conjugates GSH with leukotriene A4 to make leukotriene C4. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione is also a building block for a signaling molecule. organism: Human tissue_or_cell_type: Purified membrane enzyme experimental_model: LTC4S mutagenesis, spectroscopy and crystallography limitations: GSH participates in inflammatory mediator synthesis; biochemical use does not imply that GSH supplements cause asthma. exposure: Arg104 and Arg31 substitutions evidence_span: {"source_cache": "artifacts/glutathione-research/20980252.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5eacc338c23e1f1be126ba80eebc8ac0ce7ea8735f22a5583dcebd7ef44eded4", "start_char": 0, "end_char": 1776, "text_sha256": "5eacc338c23e1f1be126ba80eebc8ac0ce7ea8735f22a5583dcebd7ef44eded4"} [glutathione-p20980252] Arginine 104 is a key catalytic residue in leukotriene C4 synthase. (2010). https://pubmed.ncbi.nlm.nih.gov/20980252/ DOI: 10.1074/jbc.m110.105940

evidence_span

{"source_cache": "artifacts/glutathione-research/21875351.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69", "start_char": 0, "end_char": 2042, "text_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69"}

experimental_model

Randomized double-blind placebo-controlled trial

exposure

GSH 500 mg twice daily for four weeks

limitations

Trial-specific null results; not proof that every dose, duration or formulation is inactive.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

The tested supplement did not improve this measured endpoint.

primary_references

[glutathione-p21875351] Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. (2011). https://pubmed.ncbi.nlm.nih.gov/21875351/ DOI: 10.1089/acm.2010.0716

tissue_or_cell_type

40 healthy adults; 39 completed

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1165–1176

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft

### glutathione-oral-2011-dna-null The between-group change in urinary 8-OHdG was not significant (p=0.27). Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tested supplement did not improve this measured endpoint. organism: Human tissue_or_cell_type: 40 healthy adults; 39 completed experimental_model: Randomized double-blind placebo-controlled trial limitations: Trial-specific null results; not proof that every dose, duration or formulation is inactive. exposure: GSH 500 mg twice daily for four weeks evidence_span: {"source_cache": "artifacts/glutathione-research/21875351.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69", "start_char": 0, "end_char": 2042, "text_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69"} [glutathione-p21875351] Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. (2011). https://pubmed.ncbi.nlm.nih.gov/21875351/ DOI: 10.1089/acm.2010.0716

evidence_span

{"source_cache": "artifacts/glutathione-research/21875351.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69", "start_char": 0, "end_char": 2042, "text_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69"}

experimental_model

Randomized double-blind placebo-controlled trial

exposure

GSH 500 mg twice daily for four weeks

limitations

Trial-specific null results; not proof that every dose, duration or formulation is inactive.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

The tested supplement did not improve this measured endpoint.

primary_references

[glutathione-p21875351] Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. (2011). https://pubmed.ncbi.nlm.nih.gov/21875351/ DOI: 10.1089/acm.2010.0716

tissue_or_cell_type

40 healthy adults; 39 completed

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1152–1163

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft

### glutathione-oral-2011-isoprostane-null The between-group change in urinary F2-isoprostanes was not significant (p=0.38). Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tested supplement did not improve this measured endpoint. organism: Human tissue_or_cell_type: 40 healthy adults; 39 completed experimental_model: Randomized double-blind placebo-controlled trial limitations: Trial-specific null results; not proof that every dose, duration or formulation is inactive. exposure: GSH 500 mg twice daily for four weeks evidence_span: {"source_cache": "artifacts/glutathione-research/21875351.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69", "start_char": 0, "end_char": 2042, "text_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69"} [glutathione-p21875351] Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. (2011). https://pubmed.ncbi.nlm.nih.gov/21875351/ DOI: 10.1089/acm.2010.0716

evidence_span

{"source_cache": "artifacts/glutathione-research/21875351.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69", "start_char": 0, "end_char": 2042, "text_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69"}

experimental_model

Randomized double-blind placebo-controlled trial

exposure

GSH 500 mg twice daily for four weeks

limitations

Trial-specific null results; not proof that every dose, duration or formulation is inactive.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

The tested supplement did not improve this measured endpoint.

primary_references

[glutathione-p21875351] Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. (2011). https://pubmed.ncbi.nlm.nih.gov/21875351/ DOI: 10.1089/acm.2010.0716

tissue_or_cell_type

40 healthy adults; 39 completed

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1139–1150

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft

### glutathione-oral-2011-null Oral GSH did not significantly change erythrocyte reduced, oxidized or ratio glutathione measures. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tested supplement did not improve this measured endpoint. organism: Human tissue_or_cell_type: 40 healthy adults; 39 completed experimental_model: Randomized double-blind placebo-controlled trial limitations: Trial-specific null results; not proof that every dose, duration or formulation is inactive. exposure: GSH 500 mg twice daily for four weeks evidence_span: {"source_cache": "artifacts/glutathione-research/21875351.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69", "start_char": 0, "end_char": 2042, "text_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69"} [glutathione-p21875351] Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. (2011). https://pubmed.ncbi.nlm.nih.gov/21875351/ DOI: 10.1089/acm.2010.0716

evidence_span

{"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"}

experimental_model

Six-month randomized double-blind placebo-controlled trial

exposure

250 or 1000 mg/day oral GSH; one-month washout

limitations

Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

The size of the change depended on the sampled compartment.

primary_references

[glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z

tissue_or_cell_type

54 nonsmoking adults; immune subset

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1217–1228

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-month randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft

### glutathione-oral-2015-buccal High-dose buccal-cell GSH increased about 260% versus baseline at six months. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The size of the change depended on the sampled compartment. organism: Human tissue_or_cell_type: 54 nonsmoking adults; immune subset experimental_model: Six-month randomized double-blind placebo-controlled trial limitations: Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life. exposure: 250 or 1000 mg/day oral GSH; one-month washout evidence_span: {"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"} [glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z

evidence_span

{"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"}

experimental_model

Six-month randomized double-blind placebo-controlled trial

exposure

250 or 1000 mg/day oral GSH; one-month washout

limitations

Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

The measured compartment increased in the longer trial.

primary_references

[glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z

tissue_or_cell_type

54 nonsmoking adults; immune subset

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1204–1215

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-month randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft

### glutathione-oral-2015-lymphocyte At six months, high-dose lymphocyte GSH increased within the reported 30–35% range versus baseline. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured compartment increased in the longer trial. organism: Human tissue_or_cell_type: 54 nonsmoking adults; immune subset experimental_model: Six-month randomized double-blind placebo-controlled trial limitations: Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life. exposure: 250 or 1000 mg/day oral GSH; one-month washout evidence_span: {"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"} [glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z

evidence_span

{"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"}

experimental_model

Six-month randomized double-blind placebo-controlled trial

exposure

250 or 1000 mg/day oral GSH; one-month washout

limitations

Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

An immune assay changed; clinical infection protection was not established.

primary_references

[glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z

tissue_or_cell_type

54 nonsmoking adults; immune subset

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1243–1254

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-month randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft

### glutathione-oral-2015-nk At three months, high-dose NK cytotoxicity exceeded placebo by more than twofold in the immune subset. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: An immune assay changed; clinical infection protection was not established. organism: Human tissue_or_cell_type: 54 nonsmoking adults; immune subset experimental_model: Six-month randomized double-blind placebo-controlled trial limitations: Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life. exposure: 250 or 1000 mg/day oral GSH; one-month washout evidence_span: {"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"} [glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z

evidence_span

{"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"}

experimental_model

Six-month randomized double-blind placebo-controlled trial

exposure

250 or 1000 mg/day oral GSH; one-month washout

limitations

Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

The measured compartment increased in the longer trial.

primary_references

[glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z

tissue_or_cell_type

54 nonsmoking adults; immune subset

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1191–1202

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-month randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft

### glutathione-oral-2015-plasma At six months, high-dose plasma GSH increased within the reported 30–35% range versus baseline. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured compartment increased in the longer trial. organism: Human tissue_or_cell_type: 54 nonsmoking adults; immune subset experimental_model: Six-month randomized double-blind placebo-controlled trial limitations: Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life. exposure: 250 or 1000 mg/day oral GSH; one-month washout evidence_span: {"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"} [glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z

evidence_span

{"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"}

experimental_model

Six-month randomized double-blind placebo-controlled trial

exposure

250 or 1000 mg/day oral GSH; one-month washout

limitations

Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

The measured compartment increased in the longer trial.

primary_references

[glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z

tissue_or_cell_type

54 nonsmoking adults; immune subset

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1178–1189

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-month randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft

### glutathione-oral-2015-rbc At six months, high-dose erythrocyte GSH increased within the reported 30–35% range versus baseline. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured compartment increased in the longer trial. organism: Human tissue_or_cell_type: 54 nonsmoking adults; immune subset experimental_model: Six-month randomized double-blind placebo-controlled trial limitations: Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life. exposure: 250 or 1000 mg/day oral GSH; one-month washout evidence_span: {"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"} [glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z

evidence_span

{"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"}

experimental_model

Six-month randomized double-blind placebo-controlled trial

exposure

250 or 1000 mg/day oral GSH; one-month washout

limitations

Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

The observed rise was not permanently maintained after stopping.

primary_references

[glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z

tissue_or_cell_type

54 nonsmoking adults; immune subset

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1230–1241

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-month randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft

### glutathione-oral-2015-washout Measured GSH levels returned to baseline after the one-month washout. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The observed rise was not permanently maintained after stopping. organism: Human tissue_or_cell_type: 54 nonsmoking adults; immune subset experimental_model: Six-month randomized double-blind placebo-controlled trial limitations: Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life. exposure: 250 or 1000 mg/day oral GSH; one-month washout evidence_span: {"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"} [glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z

evidence_span

{"source_cache": "artifacts/glutathione-research/26891882.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "919a342fc31314fef155eba006fd5a61b2a0a2d93a02c4de5e122c3d25d690fc", "start_char": 0, "end_char": 1661, "text_sha256": "919a342fc31314fef155eba006fd5a61b2a0a2d93a02c4de5e122c3d25d690fc"}

experimental_model

Human PRDX6 structures, dimerization and mutagenesis

exposure

Leu145/Leu148 substitutions

limitations

PRDX6 peroxidase and phospholipase activities are distinct; this is not a clinical GSTP1-variant study.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

A glutathione transferase helps reactivate another peroxide-handling enzyme.

primary_references

[glutathione-p26891882] Peroxiredoxin 6 homodimerization and heterodimerization with glutathione S-transferase pi are required for its peroxidase but not phospholipase A2 activity. (2016). https://pubmed.ncbi.nlm.nih.gov/26891882/ DOI: 10.1016/j.freeradbiomed.2016.02.012

tissue_or_cell_type

Purified protein and proximity assays

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 957–968

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human PRDX6 structures, dimerization and mutagenesis · source_derived_draft · unverified_draft

### glutathione-prdx6-gstp PRDX6 heterodimerization with piGST supports glutathionylation needed in the peroxidatic cycle. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A glutathione transferase helps reactivate another peroxide-handling enzyme. organism: Human tissue_or_cell_type: Purified protein and proximity assays experimental_model: Human PRDX6 structures, dimerization and mutagenesis limitations: PRDX6 peroxidase and phospholipase activities are distinct; this is not a clinical GSTP1-variant study. exposure: Leu145/Leu148 substitutions evidence_span: {"source_cache": "artifacts/glutathione-research/26891882.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "919a342fc31314fef155eba006fd5a61b2a0a2d93a02c4de5e122c3d25d690fc", "start_char": 0, "end_char": 1661, "text_sha256": "919a342fc31314fef155eba006fd5a61b2a0a2d93a02c4de5e122c3d25d690fc"} [glutathione-p26891882] Peroxiredoxin 6 homodimerization and heterodimerization with glutathione S-transferase pi are required for its peroxidase but not phospholipase A2 activity. (2016). https://pubmed.ncbi.nlm.nih.gov/26891882/ DOI: 10.1016/j.freeradbiomed.2016.02.012

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/molybdenum-research/25777939.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1768480178724867d4c7a98f723cfd1a0010f7973eae4a4baea3d1261a06fdd2", "start_char": 0, "end_char": 2017, "text_sha256": "1768480178724867d4c7a98f723cfd1a0010f7973eae4a4baea3d1261a06fdd2"}

experimental_model

Sulfite/thiosulfate incubation of rat cortical slices and cell-free GSSG

exposure

One- versus three-hour incubations; 10 micromolar sulfite redox observations

limitations

Concentration, duration and preparation matter; GPx activity is not evidence of selenium depletion.

nutrient_topic

Molybdenum research collection; topical membership is not evidence of a direct dietary effect. · Molybdenum

organism

Rattus norvegicus; cell-free comparison

plain_language

A chemical increase in measured GSH outside cells is different from restoring a living antioxidant system.

primary_references

[mo-p25777939] In vitro evidence that sulfite impairs glutamatergic neurotransmission and inhibits glutathione metabolism-related enzymes in rat cerebral cortex. (2015). https://pubmed.ncbi.nlm.nih.gov/25777939/ DOI: 10.1016/j.ijdevneu.2015.03.005

tissue_or_cell_type

Cerebral cortex

trigger_kind

machinery_impairment Imported condition classification; unverified.

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 1431–1442

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Sulfite/thiosulfate incubation of rat cortical slices and cell-free GSSG · source_derived_draft · unverified_draft

### mo-sulfite-gssg-chemical At 500 micromolar, sulfite increased measured GSH in a cell-free GSSG solution, consistent with disulfide-bond chemistry. Condition category: machinery_impairment nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: A chemical increase in measured GSH outside cells is different from restoring a living antioxidant system. organism: Rattus norvegicus; cell-free comparison tissue_or_cell_type: Cerebral cortex experimental_model: Sulfite/thiosulfate incubation of rat cortical slices and cell-free GSSG limitations: Concentration, duration and preparation matter; GPx activity is not evidence of selenium depletion. exposure: One- versus three-hour incubations; 10 micromolar sulfite redox observations evidence_span: {"source_cache": "artifacts/molybdenum-research/25777939.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1768480178724867d4c7a98f723cfd1a0010f7973eae4a4baea3d1261a06fdd2", "start_char": 0, "end_char": 2017, "text_sha256": "1768480178724867d4c7a98f723cfd1a0010f7973eae4a4baea3d1261a06fdd2"} [mo-p25777939] In vitro evidence that sulfite impairs glutamatergic neurotransmission and inhibits glutathione metabolism-related enzymes in rat cerebral cortex. (2015). https://pubmed.ncbi.nlm.nih.gov/25777939/ DOI: 10.1016/j.ijdevneu.2015.03.005

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/molybdenum-research/33271457.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "619710a31160db0927e01193e458277773ebe5e5423629e7dab58888ab6bc617", "start_char": 0, "end_char": 1479, "text_sha256": "619710a31160db0927e01193e458277773ebe5e5423629e7dab58888ab6bc617"}

experimental_model

CRISPR SUOX/GOT1/GOT2 perturbations and sulfur-metabolite assays

exposure

Cysteine-sulfinate and H2S pathway experiments

limitations

Cell-specific contributions; a higher concentration is not a direct measurement of pathway flux.

nutrient_topic

Molybdenum research collection; topical membership is not evidence of a direct dietary effect. · Molybdenum

organism

Homo sapiens

plain_language

Glutathione and cysteine sulfur chemistry also changed.

primary_references

[mo-p33271457] The role of glutamate oxaloacetate transaminases in sulfite biosynthesis and H₂S metabolism. (2021). https://pubmed.ncbi.nlm.nih.gov/33271457/ DOI: 10.1016/j.redox.2020.101800

tissue_or_cell_type

HEK293T cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 716–727

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CRISPR SUOX/GOT1/GOT2 perturbations and sulfur-metabolite assays · source_derived_draft · unverified_draft

### mo-suox-persulfides SUOX-deficient cells accumulated persulfidated glutathione and cysteine. Condition category: machinery_impairment nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione and cysteine sulfur chemistry also changed. organism: Homo sapiens tissue_or_cell_type: HEK293T cells experimental_model: CRISPR SUOX/GOT1/GOT2 perturbations and sulfur-metabolite assays limitations: Cell-specific contributions; a higher concentration is not a direct measurement of pathway flux. exposure: Cysteine-sulfinate and H2S pathway experiments evidence_span: {"source_cache": "artifacts/molybdenum-research/33271457.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "619710a31160db0927e01193e458277773ebe5e5423629e7dab58888ab6bc617", "start_char": 0, "end_char": 1479, "text_sha256": "619710a31160db0927e01193e458277773ebe5e5423629e7dab58888ab6bc617"} [mo-p33271457] The role of glutamate oxaloacetate transaminases in sulfite biosynthesis and H₂S metabolism. (2021). https://pubmed.ncbi.nlm.nih.gov/33271457/ DOI: 10.1016/j.redox.2020.101800

cross_nutrient

true

evidence_location

Primary abstract

experimental_model

Radiolabeled sterol analysis in erythrocyte ghosts

exposure

Photooxidation followed by GSH/PHGPX.

limitations

Product co-migration and assay-specific relative kinetics; no universal cellular rate.

nutrient_topic

Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E

organism

Human-derived cell-free membranes

plain_language

The enzyme also removed peroxide groups from oxidized cholesterol, more slowly than from phospholipids in this preparation.

primary_references

[ver-thomas1990] Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. (1990). https://pubmed.ncbi.nlm.nih.gov/2294113/ DOI: 10.1016/s0021-9258(19)40252-4

tissue_or_cell_type

Erythrocyte ghosts

Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 564–576

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiolabeled sterol analysis in erythrocyte ghosts · source_derived_draft · unverified_draft

### ver-gpx4-cholesterol-hydroperoxide GSH/PHGPX reduced membrane cholesterol hydroperoxides, predominantly the photo-generated 5-alpha product, to diol-like products; cholesterol hydroperoxide decay was about one-sixth the phospholipid hydroperoxide decay rate in the ghost-membrane assay. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme also removed peroxide groups from oxidized cholesterol, more slowly than from phospholipids in this preparation. organism: Human-derived cell-free membranes tissue_or_cell_type: Erythrocyte ghosts experimental_model: Radiolabeled sterol analysis in erythrocyte ghosts limitations: Product co-migration and assay-specific relative kinetics; no universal cellular rate. exposure: Photooxidation followed by GSH/PHGPX. cross_nutrient: true evidence_location: Primary abstract [ver-thomas1990] Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. (1990). https://pubmed.ncbi.nlm.nih.gov/2294113/ DOI: 10.1016/s0021-9258(19)40252-4

cross_nutrient

true

evidence_location

Primary abstract

experimental_model

Microsomes and Triton-dispersed lipid micelles

exposure

Iron-dependent peroxidation; physiological vitamin E:phospholipid ratio as reported in abstract.

limitations

Exact concentrations are not available in the inspected abstract. Model-specific dependence does not imply every membrane requires added GPX4 to show E protection.

nutrient_topic

Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E

organism

Rattus norvegicus

plain_language

Vitamin E protection depended on peroxide removal by the GPX4/glutathione system in these preparations.

primary_references

[ver-maiorino1989] Microsomal lipid peroxidation: effect of vitamin E and its functional interaction with phospholipid hydroperoxide glutathione peroxidase. (1989). https://pubmed.ncbi.nlm.nih.gov/2586229/ DOI: 10.1007/bf02535211

tissue_or_cell_type

Liver microsomal lipids

Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 592–604

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomes and Triton-dispersed lipid micelles · source_derived_draft · unverified_draft

### ver-gpx4-gsh-tocopherol-cooperation At a physiological vitamin E-to-phospholipid ratio, inhibition of iron-dependent lipid peroxidation in rat liver microsomes and dispersed microsomal lipids was observed only when PHGPX (GPX4) and glutathione were also present. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin E protection depended on peroxide removal by the GPX4/glutathione system in these preparations. organism: Rattus norvegicus tissue_or_cell_type: Liver microsomal lipids experimental_model: Microsomes and Triton-dispersed lipid micelles limitations: Exact concentrations are not available in the inspected abstract. Model-specific dependence does not imply every membrane requires added GPX4 to show E protection. exposure: Iron-dependent peroxidation; physiological vitamin E:phospholipid ratio as reported in abstract. cross_nutrient: true evidence_location: Primary abstract [ver-maiorino1989] Microsomal lipid peroxidation: effect of vitamin E and its functional interaction with phospholipid hydroperoxide glutathione peroxidase. (1989). https://pubmed.ncbi.nlm.nih.gov/2586229/ DOI: 10.1007/bf02535211

cross_nutrient

true

evidence_location

Primary abstract

experimental_model

Rose-bengal photoperoxidation followed by enzyme treatment

exposure

GSH/PHGPX after photooxidation.

limitations

Purified-enzyme preparation; distinguishes peroxide removal from vitamin E radical trapping.

nutrient_topic

Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E

organism

Human-derived cell-free membranes

plain_language

GPX4 removed peroxide groups from membrane phospholipids using glutathione.

primary_references

[ver-thomas1990] Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. (1990). https://pubmed.ncbi.nlm.nih.gov/2294113/ DOI: 10.1016/s0021-9258(19)40252-4

tissue_or_cell_type

Erythrocyte ghosts

Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 550–562

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rose-bengal photoperoxidation followed by enzyme treatment · source_derived_draft · unverified_draft

### ver-gpx4-pl-hydroperoxide-reduction Purified PHGPX (GPX4) with glutathione reduced phospholipid hydroperoxides within photooxidized human erythrocyte ghost membranes to alcohol products without prior phospholipase cleavage. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: GPX4 removed peroxide groups from membrane phospholipids using glutathione. organism: Human-derived cell-free membranes tissue_or_cell_type: Erythrocyte ghosts experimental_model: Rose-bengal photoperoxidation followed by enzyme treatment limitations: Purified-enzyme preparation; distinguishes peroxide removal from vitamin E radical trapping. exposure: GSH/PHGPX after photooxidation. cross_nutrient: true evidence_location: Primary abstract [ver-thomas1990] Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. (1990). https://pubmed.ncbi.nlm.nih.gov/2294113/ DOI: 10.1016/s0021-9258(19)40252-4

cross_nutrient

true

evidence_location

Primary abstract

experimental_model

Sequential peroxide reduction and iron challenge

exposure

Photoperoxidation → GSH/PHGPX → iron-dependent challenge.

limitations

Ascorbate participates in this deliberately pro-oxidizing assay; this is not evidence that normal vitamin C intake damages membranes.

nutrient_topic

Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E

organism

Human-derived cell-free membranes

plain_language

Removing membrane hydroperoxides prevented an iron-driven burst of further oxidation.

primary_references

[ver-thomas1990] Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. (1990). https://pubmed.ncbi.nlm.nih.gov/2294113/ DOI: 10.1016/s0021-9258(19)40252-4

tissue_or_cell_type

Erythrocyte ghosts

Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 578–590

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Sequential peroxide reduction and iron challenge · source_derived_draft · unverified_draft

### ver-peroxide-removal-iron-burst GSH/PHGPX pretreatment completely suppressed the subsequent radical-peroxidation burst when photooxidized erythrocyte ghosts were challenged with ascorbate/iron or xanthine/xanthine-oxidase/iron. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing membrane hydroperoxides prevented an iron-driven burst of further oxidation. organism: Human-derived cell-free membranes tissue_or_cell_type: Erythrocyte ghosts experimental_model: Sequential peroxide reduction and iron challenge limitations: Ascorbate participates in this deliberately pro-oxidizing assay; this is not evidence that normal vitamin C intake damages membranes. exposure: Photoperoxidation → GSH/PHGPX → iron-dependent challenge. cross_nutrient: true evidence_location: Primary abstract [ver-thomas1990] Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. (1990). https://pubmed.ncbi.nlm.nih.gov/2294113/ DOI: 10.1016/s0021-9258(19)40252-4

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Patient-derived cell biochemistry and variant structural analysis

exposure

Compound-heterozygous GLRX5 variants

limitations

One patient; reduced succinyl-CoA contribution to ALAS2 dysfunction was proposed, not definitively isolated.

nutrient_topic

Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron

organism

Human GLRX5-deficient patient

plain_language

The defect extended beyond red-cell pigment to mitochondrial energy handling.

primary_references

[iron-p30660387] GLRX5 mutations impair heme biosynthetic enzymes ALA synthase 2 and ferrochelatase in Human congenital sideroblastic anemia. (2019). https://pubmed.ncbi.nlm.nih.gov/30660387/ DOI: 10.1016/j.ymgme.2018.12.012

tissue_or_cell_type

Lymphoblastoid and CD34-positive cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1096–1107

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient-derived cell biochemistry and variant structural analysis · source_derived_draft · unverified_draft

### iron-glrx5-energy Patient-derived cells showed reduced glutathione and aconitase activity, damaged/depleted mitochondrial DNA, lower complex I/IV activities and lower ATP content. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The defect extended beyond red-cell pigment to mitochondrial energy handling. organism: Human GLRX5-deficient patient tissue_or_cell_type: Lymphoblastoid and CD34-positive cells experimental_model: Patient-derived cell biochemistry and variant structural analysis limitations: One patient; reduced succinyl-CoA contribution to ALAS2 dysfunction was proposed, not definitively isolated. exposure: Compound-heterozygous GLRX5 variants evidence_span: {"source_cache": "artifacts/iron-research/30660387.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e", "start_char": 0, "end_char": 1625, "text_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e"} [iron-p30660387] GLRX5 mutations impair heme biosynthetic enzymes ALA synthase 2 and ferrochelatase in Human congenital sideroblastic anemia. (2019). https://pubmed.ncbi.nlm.nih.gov/30660387/ DOI: 10.1016/j.ymgme.2018.12.012

evidence_span

{"source_cache": "artifacts/nasunin-research/extract2016.publisher-abstract.txt", "locator": "Primary publisher abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "59f579b08c2eb270f935d58dfb0a751867b624b099b5eea3674abc1bb8ec0115", "start_char": 0, "end_char": 1165, "text_sha256": "59f579b08c2eb270f935d58dfb0a751867b624b099b5eea3674abc1bb8ec0115"}

experimental_model

Purified crystals versus semi-purified extracts in EPR and neutrophil assays

exposure

Chlorogenic-acid-depleted extracts; purified NAS and D3R comparisons

limitations

Mixture composition does not demonstrate pharmacological synergy. Human cells outside the body are not a clinical trial; assays differ from colon-cell ROS experiments.

nutrient_topic

Nasunin research collection; topical membership is not evidence of a direct dietary effect. · Nasunin

organism

Cell-free assays and isolated human neutrophils

plain_language

The extract result cannot be assigned entirely to nasunin.

primary_references

[nasunin-pextract2016] Characterization and antioxidant activity of semi-purified extracts and pure delphinidin-glycosides from eggplant peel ( Solanum melongena L.) (2016). https://www.sciencedirect.com/science/article/abs/pii/S1756464615005368 DOI: 10.1016/j.jff.2015.10.032

tissue_or_cell_type

Radical and luminol-amplified chemiluminescence readouts

Nasunin: identity, redox chemistry and nutrient connections (2026-09-17) · lines 640–651

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified crystals versus semi-purified extracts in EPR and neutrophil assays · source_derived_draft · unverified_draft

### nasunin-mixture-components The authors attributed additional extract activity to constituents including ascorbate and glutathione. Condition category: normal nutrient_topic: Nasunin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The extract result cannot be assigned entirely to nasunin. organism: Cell-free assays and isolated human neutrophils tissue_or_cell_type: Radical and luminol-amplified chemiluminescence readouts experimental_model: Purified crystals versus semi-purified extracts in EPR and neutrophil assays limitations: Mixture composition does not demonstrate pharmacological synergy. Human cells outside the body are not a clinical trial; assays differ from colon-cell ROS experiments. exposure: Chlorogenic-acid-depleted extracts; purified NAS and D3R comparisons evidence_span: {"source_cache": "artifacts/nasunin-research/extract2016.publisher-abstract.txt", "locator": "Primary publisher abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "59f579b08c2eb270f935d58dfb0a751867b624b099b5eea3674abc1bb8ec0115", "start_char": 0, "end_char": 1165, "text_sha256": "59f579b08c2eb270f935d58dfb0a751867b624b099b5eea3674abc1bb8ec0115"} [nasunin-pextract2016] Characterization and antioxidant activity of semi-purified extracts and pure delphinidin-glycosides from eggplant peel ( Solanum melongena L.) (2016). https://www.sciencedirect.com/science/article/abs/pii/S1756464615005368 DOI: 10.1016/j.jff.2015.10.032

evidence_span

{"source_cache": "artifacts/coumarin-research/12954377.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3cfcf94368e2f91bed45cd7901678e6db02567ac1c8e7d8b8c78bae52932d76f", "start_char": 0, "end_char": 1196, "text_sha256": "3cfcf94368e2f91bed45cd7901678e6db02567ac1c8e7d8b8c78bae52932d76f"}

experimental_model

HPLC isolation with mass spectrometry and NMR characterization

exposure

Purification of coumarin epoxide glutathione conjugate

limitations

Analytical identification does not establish protection by oral glutathione.

nutrient_topic

Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin

organism

Hepatic microsomal preparations; species detailed in original paper

plain_language

Glutathione can become chemically attached to this reactive metabolite.

primary_references

[coumarin-p12954377] Liquid chromatographic determination of the glutathione conjugate and ring-opened metabolites formed from coumarin epoxidation. (2003). https://pubmed.ncbi.nlm.nih.gov/12954377/ DOI: 10.1016/s1570-0232(03)00473-2

tissue_or_cell_type

In vitro metabolism mixtures

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 280–291

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HPLC isolation with mass spectrometry and NMR characterization · source_derived_draft · unverified_draft

### coumarin-conjugate-identity The coumarin epoxide glutathione conjugate was isolated and structurally characterized, with glutathione attached at position 3. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione can become chemically attached to this reactive metabolite. organism: Hepatic microsomal preparations; species detailed in original paper tissue_or_cell_type: In vitro metabolism mixtures experimental_model: HPLC isolation with mass spectrometry and NMR characterization limitations: Analytical identification does not establish protection by oral glutathione. exposure: Purification of coumarin epoxide glutathione conjugate evidence_span: {"source_cache": "artifacts/coumarin-research/12954377.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3cfcf94368e2f91bed45cd7901678e6db02567ac1c8e7d8b8c78bae52932d76f", "start_char": 0, "end_char": 1196, "text_sha256": "3cfcf94368e2f91bed45cd7901678e6db02567ac1c8e7d8b8c78bae52932d76f"} [coumarin-p12954377] Liquid chromatographic determination of the glutathione conjugate and ring-opened metabolites formed from coumarin epoxidation. (2003). https://pubmed.ncbi.nlm.nih.gov/12954377/ DOI: 10.1016/s1570-0232(03)00473-2

evidence_span

{"source_cache": "artifacts/coumarin-research/15141102.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5", "start_char": 0, "end_char": 2618, "text_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5"}

experimental_model

Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols

exposure

Controlled epoxide generation with cofactors supplied

limitations

Cell-free species comparison does not quantify human dietary injury risk or supplement benefit.

nutrient_topic

Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin

organism

Human pooled cytosols, F344 rat and B6C3F1 mouse

plain_language

Glutathione captures the epoxide in the rodent preparations.

primary_references

[coumarin-p15141102] Metabolic detoxification determines species differences in coumarin-induced hepatotoxicity. (2004). https://pubmed.ncbi.nlm.nih.gov/15141102/ DOI: 10.1093/toxsci/kfh162

tissue_or_cell_type

Liver cytosolic detoxification system

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 488–499

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols · source_derived_draft · unverified_draft

### coumarin-gst-conjugation Rat and mouse cytosols conjugated the epoxide with glutathione through enzymatic and nonenzymatic routes. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione captures the epoxide in the rodent preparations. organism: Human pooled cytosols, F344 rat and B6C3F1 mouse tissue_or_cell_type: Liver cytosolic detoxification system experimental_model: Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols limitations: Cell-free species comparison does not quantify human dietary injury risk or supplement benefit. exposure: Controlled epoxide generation with cofactors supplied evidence_span: {"source_cache": "artifacts/coumarin-research/15141102.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5", "start_char": 0, "end_char": 2618, "text_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5"} [coumarin-p15141102] Metabolic detoxification determines species differences in coumarin-induced hepatotoxicity. (2004). https://pubmed.ncbi.nlm.nih.gov/15141102/ DOI: 10.1093/toxsci/kfh162

evidence_span

{"source_cache": "artifacts/coumarin-research/15141102.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5", "start_char": 0, "end_char": 2618, "text_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5"}

experimental_model

Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols

exposure

Controlled epoxide generation with cofactors supplied

limitations

Cell-free species comparison does not quantify human dietary injury risk or supplement benefit.

nutrient_topic

Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin

organism

Human pooled cytosols, F344 rat and B6C3F1 mouse

plain_language

Glutathione capture was not the dominant measured human route.

primary_references

[coumarin-p15141102] Metabolic detoxification determines species differences in coumarin-induced hepatotoxicity. (2004). https://pubmed.ncbi.nlm.nih.gov/15141102/ DOI: 10.1093/toxsci/kfh162

tissue_or_cell_type

Liver cytosolic detoxification system

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 514–525

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols · source_derived_draft · unverified_draft

### coumarin-human-route-partition With cofactors supplied, human cytosolic products were approximately 90% o-HPAA and 10% glutathione conjugate. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione capture was not the dominant measured human route. organism: Human pooled cytosols, F344 rat and B6C3F1 mouse tissue_or_cell_type: Liver cytosolic detoxification system experimental_model: Coumarin epoxide generated with mouse microsomes plus species-specific liver cytosols limitations: Cell-free species comparison does not quantify human dietary injury risk or supplement benefit. exposure: Controlled epoxide generation with cofactors supplied evidence_span: {"source_cache": "artifacts/coumarin-research/15141102.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5", "start_char": 0, "end_char": 2618, "text_sha256": "2ddbcb7b41520d3405b9abe3ed8b492c5a6063e88d52c549481d444dcd541dc5"} [coumarin-p15141102] Metabolic detoxification determines species differences in coumarin-induced hepatotoxicity. (2004). https://pubmed.ncbi.nlm.nih.gov/15141102/ DOI: 10.1093/toxsci/kfh162

experimental_model

Animal selenium status and erythrocyte glutathione-peroxidase biochemistry.

limitations

This experiment-specific relationship does not establish a human dietary-deficiency threshold or supplementation benefit.

organism

Rat

Selenium: literature corrections and mechanism additions · lines 954–963

Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Animal selenium status and erythrocyte glutathione-peroxidase biochemistry. · secondary_verified · secondary_verified

## gpx1-peroxide-reduction GPX1 uses glutathione to remove hydrogen peroxide. Classical GPX1 couples hydrogen-peroxide reduction to oxidation of reduced glutathione; water and glutathione disulfide are products. Experimental model: Animal selenium status and erythrocyte glutathione-peroxidase biochemistry. Organism: Rat Limitations: This experiment-specific relationship does not establish a human dietary-deficiency threshold or supplementation benefit. Primary reference: [Selenium: biochemical role as a component of glutathione peroxidase](https://pubmed.ncbi.nlm.nih.gov/4686466/)

cell_type

MCF-7 transfectants

experimental_model

GPX2 cDNA expression and enzyme assays

limitations

Expression model; not an intestinal clinical outcome.

organism

human

Selenium: literature corrections and mechanism additions · lines 642–652

Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · GPX2 cDNA expression and enzyme assays · secondary_verified · secondary_verified

## gpx2-reduces-peroxide GPX2 can remove peroxide using glutathione. Expressed human GPX2 exhibited glutathione-dependent hydrogen-peroxide reduction. Organism: human Cell type: MCF-7 transfectants Experimental model: GPX2 cDNA expression and enzyme assays Limitations: Expression model; not an intestinal clinical outcome. Primary reference: [Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI](https://pubmed.ncbi.nlm.nih.gov/8428933/)

cell_type

plasma

experimental_model

Purified enzyme kinetics

limitations

Assay glutathione availability does not define every physiological electron donor.

organism

human

Selenium: literature corrections and mechanism additions · lines 678–688

Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Purified enzyme kinetics · secondary_verified · secondary_verified

## gpx3-reduces-extracellular-peroxide GPX3 can remove peroxide outside cells. Purified human plasma glutathione peroxidase reduced hydrogen peroxide using glutathione. Organism: human Cell type: plasma Experimental model: Purified enzyme kinetics Limitations: Assay glutathione availability does not define every physiological electron donor. Primary reference: [Characterization of the major hydroperoxide-reducing activity of human plasma. Purification and properties of a selenium-dependent glutathione peroxidase.](https://www.sciencedirect.com/science/article/pii/S0021925818453926)