Human copper-zinc superoxide dismutase / SOD1

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Regional cerebral blood flow measurement in rats with nitric oxide metabolite and hydroxyl radical assays

exposure

Oxygen at 5 atmospheres absolute for 30 minutes, with L-NAME, a nitric oxide donor, or intravascular superoxide dismutase

limitations

Five atmospheres is well above therapeutic pressure and was chosen to study oxygen toxicity. The superoxide dismutase rescue is the key mechanistic step.

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

Rat

plain_language

Giving the enzyme that clears superoxide kept the vessels open.

primary_references

[hbot-p11139368] Hyperbaric oxygen reduces cerebral blood flow by inactivating nitric oxide. (2000). https://pubmed.ncbi.nlm.nih.gov/11139368/ DOI: 10.1006/niox.2000.0313

tissue_or_cell_type

Brain

trigger_kind

machinery_impairment Imported condition classification; unverified.

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 179–190

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Regional cerebral blood flow measurement in rats with nitric oxide metabolite and hydroxyl radical assays · source_derived_draft · unverified_draft

### hbot-sod-rescue Administration of superoxide dismutase into the circulation before exposure completely abolished the decrease in regional cerebral blood flow at 5 ATA. Condition category: machinery_impairment 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: Giving the enzyme that clears superoxide kept the vessels open. organism: Rat tissue_or_cell_type: Brain experimental_model: Regional cerebral blood flow measurement in rats with nitric oxide metabolite and hydroxyl radical assays limitations: Five atmospheres is well above therapeutic pressure and was chosen to study oxygen toxicity. The superoxide dismutase rescue is the key mechanistic step. exposure: Oxygen at 5 atmospheres absolute for 30 minutes, with L-NAME, a nitric oxide donor, or intravascular superoxide dismutase evidence_span: {"source_cache": "artifacts/hbot-research/11139368.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9823a7f177483257b812d7c8c8e8052c3f04d6a7aa052876369c7c64b55668f3", "start_char": 0, "end_char": 1672, "text_sha256": "9823a7f177483257b812d7c8c8e8052c3f04d6a7aa052876369c7c64b55668f3"} [hbot-p11139368] Hyperbaric oxygen reduces cerebral blood flow by inactivating nitric oxide. (2000). https://pubmed.ncbi.nlm.nih.gov/11139368/ DOI: 10.1006/niox.2000.0313

cross_nutrient

Copper and zinc cofactor identity in SOD1 is distinguished from Mn-dependent SOD2.

experimental_model

NMR of copper-depleted human SOD1 C6A/C111S preparation

exposure

Copper-depleted zinc-containing disulfide-reduced preparation

limitations

The study structurally examined the C6A/C111S copper-depleted, zinc-containing preparation. This identity statement does not assert Mn can replace either SOD1 metal.

nutrient_topic

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

organism

Homo sapiens protein

plain_language

SOD1 and SOD2 use different metals.

primary_references

[mn-enz-16291742] Human SOD1 before harboring the catalytic metal: solution structure of copper-depleted, disulfide-reduced form. (2006). https://pubmed.ncbi.nlm.nih.gov/16291742/ DOI: 10.1074/jbc.m506497200

tissue_or_cell_type

Purified SOD1

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 458–469

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · NMR of copper-depleted human SOD1 C6A/C111S preparation · source_derived_draft · unverified_draft

### mn-enz-sod1-distinct-metals Human SOD1 maturation involves copper and zinc insertion and a Cys57–Cys146 disulfide; this is a different metalloprotein system from manganese SOD2. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: SOD1 and SOD2 use different metals. organism: Homo sapiens protein tissue_or_cell_type: Purified SOD1 experimental_model: NMR of copper-depleted human SOD1 C6A/C111S preparation limitations: The study structurally examined the C6A/C111S copper-depleted, zinc-containing preparation. This identity statement does not assert Mn can replace either SOD1 metal. exposure: Copper-depleted zinc-containing disulfide-reduced preparation cross_nutrient: Copper and zinc cofactor identity in SOD1 is distinguished from Mn-dependent SOD2. [mn-enz-16291742] Human SOD1 before harboring the catalytic metal: solution structure of copper-depleted, disulfide-reduced form. (2006). https://pubmed.ncbi.nlm.nih.gov/16291742/ DOI: 10.1074/jbc.m506497200

evidence_access

Primary full text

experimental_model

Human HUVECs, 0.5 mM silicon preparation.

limitations

Expression is not measured catalytic flux or proof that silicon replaces established metal cofactors.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

An individual antioxidant or vascular enzyme was measured.

primary_references

Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30062712/ · DOI 10.1002/term.2744

Silica: soluble silicon, cellular transport and particle-specific 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 · Human HUVECs, 0.5 mM silicon preparation. · source_derived_draft · unverified_draft

## silica-endothelial-sod1 An individual antioxidant or vascular enzyme was measured. Silicon-treated HUVECs increased SOD1 mRNA under the reported normal and peroxide conditions. Model: Human HUVECs, 0.5 mM silicon preparation. Limitations: Expression is not measured catalytic flux or proof that silicon replaces established metal cofactors. Evidence access: Primary full text Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30062712/ · DOI 10.1002/term.2744

evidence_span

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experimental_model

Refinement of the 2 angstrom crystal structure of copper, zinc superoxide dismutase with molecular surface analysis

exposure

Structural and mechanistic analysis of the active site

limitations

Structural chemistry. It explains why the enzyme needs its metals; it is not a statement about dietary copper or zinc.

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

Bovine enzyme structure

plain_language

The copper atom itself is what takes and gives back the electron.

primary_references

[hbot-p6316150] Structure and mechanism of copper, zinc superoxide dismutase. (1983). https://pubmed.ncbi.nlm.nih.gov/6316150/ DOI: 10.1038/306284a0

tissue_or_cell_type

Purified enzyme

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 491–502

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Refinement of the 2 angstrom crystal structure of copper, zinc superoxide dismutase with molecular surface analysis · source_derived_draft · unverified_draft

### hbot-sod1-copper-mechanism Copper, zinc superoxide dismutase catalyses the two-step dismutation of superoxide to molecular oxygen and hydrogen peroxide through alternate reduction and oxidation of the active-site copper, with a single complementary binding position for superoxide at the Cu(II) and the activity-important Arg141. 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 copper atom itself is what takes and gives back the electron. organism: Bovine enzyme structure tissue_or_cell_type: Purified enzyme experimental_model: Refinement of the 2 angstrom crystal structure of copper, zinc superoxide dismutase with molecular surface analysis limitations: Structural chemistry. It explains why the enzyme needs its metals; it is not a statement about dietary copper or zinc. exposure: Structural and mechanistic analysis of the active site evidence_span: {"source_cache": "artifacts/hbot-research/6316150.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dc20323f9774c6c743e01f8bdbeedbc42b0ddac982f1e17d53a9591b87bf5379", "start_char": 0, "end_char": 867, "text_sha256": "dc20323f9774c6c743e01f8bdbeedbc42b0ddac982f1e17d53a9591b87bf5379"} [hbot-p6316150] Structure and mechanism of copper, zinc superoxide dismutase. (1983). https://pubmed.ncbi.nlm.nih.gov/6316150/ DOI: 10.1038/306284a0

cross_nutrient

true

experimental_model

Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR

exposure

Human CCS domain constructs and SOD1; ESI-MS and NMR.

limitations

Reconstituted human proteins studied in vitro; domain contributions do not imply CCS carries zinc to SOD1 or that zinc supplementation completes copper loading.

nutrient_topic

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

organism

Homo sapiens

plain_language

SOD1 needs copper delivery as well as zinc binding.

primary_references

[zinc-enz-ccs-2012] Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS). (2012). https://pubmed.ncbi.nlm.nih.gov/22869735/ DOI: 10.1073/pnas.1207493109

tissue_or_cell_type

Purified protein; cell-free assay

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 690–701

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR · source_derived_draft · unverified_draft

### zinc-enz-ccs-copper In the purified human protein system, CCS domain 1 was necessary for loading SOD1 with Cu(I). Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: SOD1 needs copper delivery as well as zinc binding. organism: Homo sapiens tissue_or_cell_type: Purified protein; cell-free assay experimental_model: Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR limitations: Reconstituted human proteins studied in vitro; domain contributions do not imply CCS carries zinc to SOD1 or that zinc supplementation completes copper loading. exposure: Human CCS domain constructs and SOD1; ESI-MS and NMR. cross_nutrient: true [zinc-enz-ccs-2012] Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS). (2012). https://pubmed.ncbi.nlm.nih.gov/22869735/ DOI: 10.1073/pnas.1207493109

cross_nutrient

true

experimental_model

Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR

exposure

Human CCS mutants/domain constructs examined by ESI-MS and NMR.

limitations

Reconstituted human proteins studied in vitro; domain contributions do not imply CCS carries zinc to SOD1 or that zinc supplementation completes copper loading.

nutrient_topic

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

organism

Homo sapiens

plain_language

SOD1 maturation also requires forming a specific internal disulfide bond.

primary_references

[zinc-enz-ccs-2012] Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS). (2012). https://pubmed.ncbi.nlm.nih.gov/22869735/ DOI: 10.1073/pnas.1207493109

tissue_or_cell_type

Purified protein; cell-free assay

Zinc: transport, enzyme loading, deficiency 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 · Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR · source_derived_draft · unverified_draft

### zinc-enz-ccs-disulfide Human CCS domain 3 catalyzed formation of the SOD1 Cys57-Cys146 disulfide through a transfer mechanism involving CCS Cys244 and Cys246. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: SOD1 maturation also requires forming a specific internal disulfide bond. organism: Homo sapiens tissue_or_cell_type: Purified protein; cell-free assay experimental_model: Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR limitations: Reconstituted human proteins studied in vitro; domain contributions do not imply CCS carries zinc to SOD1 or that zinc supplementation completes copper loading. exposure: Human CCS mutants/domain constructs examined by ESI-MS and NMR. cross_nutrient: true [zinc-enz-ccs-2012] Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS). (2012). https://pubmed.ncbi.nlm.nih.gov/22869735/ DOI: 10.1073/pnas.1207493109

cross_nutrient

true

experimental_model

Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR

exposure

Full-length and domain-truncated human CCS with human SOD1.

limitations

Reconstituted human proteins studied in vitro; domain contributions do not imply CCS carries zinc to SOD1 or that zinc supplementation completes copper loading.

nutrient_topic

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

organism

Homo sapiens

plain_language

The copper-delivery protein first has to engage SOD1.

primary_references

[zinc-enz-ccs-2012] Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS). (2012). https://pubmed.ncbi.nlm.nih.gov/22869735/ DOI: 10.1073/pnas.1207493109

tissue_or_cell_type

Purified protein; cell-free assay

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 703–714

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR · source_derived_draft · unverified_draft

### zinc-enz-ccs-recognition Human CCS domain 2 promoted the CCS-SOD1 heterodimer interaction required for copper loading in the in-vitro study. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The copper-delivery protein first has to engage SOD1. organism: Homo sapiens tissue_or_cell_type: Purified protein; cell-free assay experimental_model: Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR limitations: Reconstituted human proteins studied in vitro; domain contributions do not imply CCS carries zinc to SOD1 or that zinc supplementation completes copper loading. exposure: Full-length and domain-truncated human CCS with human SOD1. cross_nutrient: true [zinc-enz-ccs-2012] Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS). (2012). https://pubmed.ncbi.nlm.nih.gov/22869735/ DOI: 10.1073/pnas.1207493109

cross_nutrient

true

experimental_model

Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR

exposure

10 µM ZnSO4 in expression medium; 100 µM CuCl2 added after 48 h and incubated 24 h.

limitations

HEK293T cells overexpressed SOD1/CCS above endogenous levels; these medium concentrations are experimental exposures, not dietary targets. Copper transfer and disulfide oxidation need not occur in a fixed coupled step in every cellular context.

nutrient_topic

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

organism

Homo sapiens

plain_language

The copper chaperone increased copper loading into zinc-containing SOD1.

primary_references

[zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202

tissue_or_cell_type

Human HEK293T cytoplasm

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 742–753

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR · source_derived_draft · unverified_draft

### zinc-enz-sod1-copper-loading Coexpression of CCS increased Cu(I) incorporation into SOD1 after Cu(II) exposure in zinc-supplemented HEK293T cells; at higher expression the Cu(I),Zn-SOD1:E,Zn-SOD1 ratio reached about 1:1. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The copper chaperone increased copper loading into zinc-containing SOD1. organism: Homo sapiens tissue_or_cell_type: Human HEK293T cytoplasm experimental_model: Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR limitations: HEK293T cells overexpressed SOD1/CCS above endogenous levels; these medium concentrations are experimental exposures, not dietary targets. Copper transfer and disulfide oxidation need not occur in a fixed coupled step in every cellular context. exposure: 10 µM ZnSO4 in expression medium; 100 µM CuCl2 added after 48 h and incubated 24 h. cross_nutrient: true [zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202

duration

Not stated here

evidence_access

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

experimental_model

RAW 264.7 murine macrophages

exposure

(+)-Lariciresinol

limitations

Expression levels, not enzyme activity assays.

organism

RAW 264.7 murine macrophages

plain_language

(+)-Lariciresinol raised superoxide dismutase, glutathione peroxidase and catalase at transcript and protein level.

primary_references

Antioxidant efficacy and the upregulation of Nrf2-mediated HO-1 expression by (+)-lariciresinol, a lignan isolated from Rubia philippinensis, through the activation of p38. (2017). https://pubmed.ncbi.nlm.nih.gov/28378774/ DOI: 10.1038/srep46035

route

In vitro

tissue

Antioxidant enzyme expression

Lariciresinol: five molecules under one name, and the mechanisms each one carries (2026-09-22) · lines 55–64

Original AI-assisted curation of twelve primary studies, every abstract read and all DOIs cross-checked against live PubMed metadata. Mechanism edges only, with no conclusion or claim of benefit recorded. Three author clusters account for eight of the twelve and carry shared laboratory keys. Study-specific concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## plus-lariciresinol-raises-antioxidant-enzymes (+)-Lariciresinol raised superoxide dismutase, glutathione peroxidase and catalase at transcript and protein level. Model/species: RAW 264.7 murine macrophages Tissue/system: Antioxidant enzyme expression Exposure: (+)-Lariciresinol Route: In vitro Duration: Not stated here Limits: Expression levels, not enzyme activity assays. Primary reference: Antioxidant efficacy and the upregulation of Nrf2-mediated HO-1 expression by (+)-lariciresinol, a lignan isolated from Rubia philippinensis, through the activation of p38. (2017). https://pubmed.ncbi.nlm.nih.gov/28378774/ DOI: 10.1038/srep46035 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_span

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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 cell’s own defence enzymes measured lower, not higher, after repeated sessions.

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 244–255

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-antioxidant-sod After fifteen sessions, erythrocyte superoxide dismutase activity fell significantly compared with the first exposure. 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 cell’s own defence enzymes measured lower, not higher, after repeated sessions. 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

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experimental_model

Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement

exposure

100% oxygen at 2.5 ATA for three 20-minute periods

limitations

A human exposure study with a within-subject design. The iron-sequestration explanation is the authors’ inference from the pattern of protection, not a direct measurement of free iron.

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

Only one defence protein went up, and it is the one that handles heme iron.

primary_references

[hbot-p11023535] Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. (2000). https://pubmed.ncbi.nlm.nih.gov/11023535/ DOI: 10.1093/carcin/21.10.1795

tissue_or_cell_type

Circulating lymphocytes

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 309–320

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement · source_derived_draft · unverified_draft

### hbot-ho1-induction Heme oxygenase-1 levels were increased in lymphocytes 24 hours after treatment, while superoxide dismutase, catalase and the DNA repair enzymes apurinic endonuclease and DNA polymerase beta were not enhanced in expression. 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: Only one defence protein went up, and it is the one that handles heme iron. organism: Human tissue_or_cell_type: Circulating lymphocytes experimental_model: Comet assay in lymphocytes of volunteers before and after hyperbaric oxygen, with enzyme expression measurement limitations: A human exposure study with a within-subject design. The iron-sequestration explanation is the authors’ inference from the pattern of protection, not a direct measurement of free iron. exposure: 100% oxygen at 2.5 ATA for three 20-minute periods evidence_span: {"source_cache": "artifacts/hbot-research/11023535.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d", "start_char": 0, "end_char": 1576, "text_sha256": "19b770dff3d327e2dd6d49180686f9823624190ab5693c28b88adcfaf703f14d"} [hbot-p11023535] Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. (2000). https://pubmed.ncbi.nlm.nih.gov/11023535/ DOI: 10.1093/carcin/21.10.1795

evidence_span

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experimental_model

Regional cerebral blood flow measurement in rats with nitric oxide metabolite and hydroxyl radical assays

exposure

Oxygen at 5 atmospheres absolute for 30 minutes, with L-NAME, a nitric oxide donor, or intravascular superoxide dismutase

limitations

Five atmospheres is well above therapeutic pressure and was chosen to study oxygen toxicity. The superoxide dismutase rescue is the key mechanistic step.

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

Rat

plain_language

Superoxide destroys the molecule that keeps vessels relaxed, and removing superoxide removes the effect.

primary_references

[hbot-p11139368] Hyperbaric oxygen reduces cerebral blood flow by inactivating nitric oxide. (2000). https://pubmed.ncbi.nlm.nih.gov/11139368/ DOI: 10.1006/niox.2000.0313

tissue_or_cell_type

Brain

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 166–177

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Regional cerebral blood flow measurement in rats with nitric oxide metabolite and hydroxyl radical assays · source_derived_draft · unverified_draft

### hbot-no-inactivation Brain nitric oxide metabolite levels fell by 31% and correlated with the fall in blood flow, while estimated hydroxyl radical production rose by 56%, and the blood-flow decrease was completely abolished by intravascular superoxide dismutase. 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: Superoxide destroys the molecule that keeps vessels relaxed, and removing superoxide removes the effect. organism: Rat tissue_or_cell_type: Brain experimental_model: Regional cerebral blood flow measurement in rats with nitric oxide metabolite and hydroxyl radical assays limitations: Five atmospheres is well above therapeutic pressure and was chosen to study oxygen toxicity. The superoxide dismutase rescue is the key mechanistic step. exposure: Oxygen at 5 atmospheres absolute for 30 minutes, with L-NAME, a nitric oxide donor, or intravascular superoxide dismutase evidence_span: {"source_cache": "artifacts/hbot-research/11139368.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9823a7f177483257b812d7c8c8e8052c3f04d6a7aa052876369c7c64b55668f3", "start_char": 0, "end_char": 1672, "text_sha256": "9823a7f177483257b812d7c8c8e8052c3f04d6a7aa052876369c7c64b55668f3"} [hbot-p11139368] Hyperbaric oxygen reduces cerebral blood flow by inactivating nitric oxide. (2000). https://pubmed.ncbi.nlm.nih.gov/11139368/ DOI: 10.1006/niox.2000.0313

evidence_span

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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

The cell rebuilt exactly three proteins: the heme enzyme, the manganese enzyme and the selenium enzyme.

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 426–437

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-mrna-response Messenger RNA for heme oxygenase-1, manganese superoxide dismutase and cytoplasmic thioredoxin reductase 1 rose three- to six-fold nine hours after exposure, with heme oxygenase-1 rising a few hours before manganese superoxide dismutase, while catalase, copper-zinc superoxide dismutase, glutathione reductase, glutathione peroxidase and thioredoxin did not change. 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 cell rebuilt exactly three proteins: the heme enzyme, the manganese enzyme and the selenium enzyme. 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

cross_nutrient

true

experimental_model

Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR

exposure

10 µM ZnSO4 and SOD1/CCS coexpression; no added CuCl2 in this comparison.

limitations

HEK293T cells overexpressed SOD1/CCS above endogenous levels; these medium concentrations are experimental exposures, not dietary targets. Copper transfer and disulfide oxidation need not occur in a fixed coupled step in every cellular context. This is not proof that all copper is absent from the cell.

nutrient_topic

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

organism

Homo sapiens

plain_language

CCS can help form the SOD1 disulfide before copper is inserted.

primary_references

[zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202

tissue_or_cell_type

Human HEK293T cytoplasm

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 755–766

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR · source_derived_draft · unverified_draft

### zinc-enz-sod1-disulfide-independent In zinc-supplemented HEK293T cells, CCS coexpression promoted SOD1 disulfide oxidation without detectable additional SOD1 copper loading. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: CCS can help form the SOD1 disulfide before copper is inserted. organism: Homo sapiens tissue_or_cell_type: Human HEK293T cytoplasm experimental_model: Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR limitations: HEK293T cells overexpressed SOD1/CCS above endogenous levels; these medium concentrations are experimental exposures, not dietary targets. Copper transfer and disulfide oxidation need not occur in a fixed coupled step in every cellular context. This is not proof that all copper is absent from the cell. exposure: 10 µM ZnSO4 and SOD1/CCS coexpression; no added CuCl2 in this comparison. cross_nutrient: true [zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202

cross_nutrient

false

experimental_model

Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR

exposure

10 µM ZnSO4 immediately after transfection; 48 h expression before later copper manipulations.

limitations

HEK293T cells overexpressed SOD1/CCS above endogenous levels; these medium concentrations are experimental exposures, not dietary targets. Copper transfer and disulfide oxidation need not occur in a fixed coupled step in every cellular context.

nutrient_topic

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

organism

Homo sapiens

plain_language

Zinc binding helps the cellular SOD1 protein reach a dimeric maturation intermediate.

primary_references

[zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202

tissue_or_cell_type

Human HEK293T cytoplasm

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 729–740

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR · source_derived_draft · unverified_draft

### zinc-enz-sod1-zinc-binding Adding 10 µM ZnSO4 during human SOD1 expression in HEK293T cells promoted site-selective binding of one zinc ion per SOD1 subunit and the zinc-containing dimer. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc binding helps the cellular SOD1 protein reach a dimeric maturation intermediate. organism: Homo sapiens tissue_or_cell_type: Human HEK293T cytoplasm experimental_model: Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR limitations: HEK293T cells overexpressed SOD1/CCS above endogenous levels; these medium concentrations are experimental exposures, not dietary targets. Copper transfer and disulfide oxidation need not occur in a fixed coupled step in every cellular context. exposure: 10 µM ZnSO4 immediately after transfection; 48 h expression before later copper manipulations. cross_nutrient: false [zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202

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