Coumarin 3,4-epoxide

evidence_span

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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

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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

The short-lived epoxide can become an aldehyde.

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 475–486

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-epoxide-rearrangement Coumarin 3,4-epoxide can rearrange spontaneously to the reactive aldehyde o-HPA. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The short-lived epoxide can become an aldehyde. 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

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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

evidence_span

{"source_cache": "artifacts/coumarin-research/11950775.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861", "start_char": 0, "end_char": 1158, "text_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861"}

experimental_model

Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments

exposure

CYP1A/2E antibody inhibition and 5-phenyl-pentyne lung experiments

limitations

Relative contributions depend on species and tissue; this is not a clinical drug-interaction study.

nutrient_topic

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

organism

Human, rat and mouse; each claim specifies enzyme origin

plain_language

CYP1A1 can route coumarin toward a reactive intermediate.

primary_references

[coumarin-p11950775] Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. (2002). https://pubmed.ncbi.nlm.nih.gov/11950775/ DOI: 10.1124/dmd.30.5.483

tissue_or_cell_type

Liver and lung microsomes

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 215–226

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments · source_derived_draft · unverified_draft

### coumarin-1a1-epoxide Recombinant human CYP1A enzymes catalyzed coumarin epoxidation; CYP1A1 was among the tested human forms. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP1A1 can route coumarin toward a reactive intermediate. organism: Human, rat and mouse; each claim specifies enzyme origin tissue_or_cell_type: Liver and lung microsomes experimental_model: Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments limitations: Relative contributions depend on species and tissue; this is not a clinical drug-interaction study. exposure: CYP1A/2E antibody inhibition and 5-phenyl-pentyne lung experiments evidence_span: {"source_cache": "artifacts/coumarin-research/11950775.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861", "start_char": 0, "end_char": 1158, "text_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861"} [coumarin-p11950775] Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. (2002). https://pubmed.ncbi.nlm.nih.gov/11950775/ DOI: 10.1124/dmd.30.5.483

evidence_span

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experimental_model

Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments

exposure

CYP1A/2E antibody inhibition and 5-phenyl-pentyne lung experiments

limitations

Relative contributions depend on species and tissue; this is not a clinical drug-interaction study.

nutrient_topic

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

organism

Human, rat and mouse; each claim specifies enzyme origin

plain_language

CYP1A2 provides another route to the reactive intermediate.

primary_references

[coumarin-p11950775] Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. (2002). https://pubmed.ncbi.nlm.nih.gov/11950775/ DOI: 10.1124/dmd.30.5.483

tissue_or_cell_type

Liver and lung microsomes

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 228–239

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments · source_derived_draft · unverified_draft

### coumarin-1a2-epoxide Recombinant human CYP1A2 catalyzed coumarin 3,4-epoxide formation. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP1A2 provides another route to the reactive intermediate. organism: Human, rat and mouse; each claim specifies enzyme origin tissue_or_cell_type: Liver and lung microsomes experimental_model: Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments limitations: Relative contributions depend on species and tissue; this is not a clinical drug-interaction study. exposure: CYP1A/2E antibody inhibition and 5-phenyl-pentyne lung experiments evidence_span: {"source_cache": "artifacts/coumarin-research/11950775.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861", "start_char": 0, "end_char": 1158, "text_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861"} [coumarin-p11950775] Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. (2002). https://pubmed.ncbi.nlm.nih.gov/11950775/ DOI: 10.1124/dmd.30.5.483

evidence_span

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experimental_model

Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments

exposure

CYP1A/2E antibody inhibition and 5-phenyl-pentyne lung experiments

limitations

Relative contributions depend on species and tissue; this is not a clinical drug-interaction study.

nutrient_topic

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

organism

Human, rat and mouse; each claim specifies enzyme origin

plain_language

CYP2E1 also produces the reactive intermediate.

primary_references

[coumarin-p11950775] Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. (2002). https://pubmed.ncbi.nlm.nih.gov/11950775/ DOI: 10.1124/dmd.30.5.483

tissue_or_cell_type

Liver and lung microsomes

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 241–252

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments · source_derived_draft · unverified_draft

### coumarin-2e1-epoxide Recombinant human CYP2E1 catalyzed coumarin 3,4-epoxide formation. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP2E1 also produces the reactive intermediate. organism: Human, rat and mouse; each claim specifies enzyme origin tissue_or_cell_type: Liver and lung microsomes experimental_model: Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments limitations: Relative contributions depend on species and tissue; this is not a clinical drug-interaction study. exposure: CYP1A/2E antibody inhibition and 5-phenyl-pentyne lung experiments evidence_span: {"source_cache": "artifacts/coumarin-research/11950775.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861", "start_char": 0, "end_char": 1158, "text_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861"} [coumarin-p11950775] Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. (2002). https://pubmed.ncbi.nlm.nih.gov/11950775/ DOI: 10.1124/dmd.30.5.483

evidence_span

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experimental_model

Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments

exposure

CYP1A/2E antibody inhibition and 5-phenyl-pentyne lung experiments

limitations

Relative contributions depend on species and tissue; this is not a clinical drug-interaction study.

nutrient_topic

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

organism

Human, rat and mouse; each claim specifies enzyme origin

plain_language

Mouse lung has a tissue-specific activation route.

primary_references

[coumarin-p11950775] Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. (2002). https://pubmed.ncbi.nlm.nih.gov/11950775/ DOI: 10.1124/dmd.30.5.483

tissue_or_cell_type

Liver and lung microsomes

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 254–265

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments · source_derived_draft · unverified_draft

### coumarin-mouse-lung-epoxide Inhibitor experiments attributed up to 67% of whole-mouse-lung microsomal epoxidation to CYP2F2. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mouse lung has a tissue-specific activation route. organism: Human, rat and mouse; each claim specifies enzyme origin tissue_or_cell_type: Liver and lung microsomes experimental_model: Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments limitations: Relative contributions depend on species and tissue; this is not a clinical drug-interaction study. exposure: CYP1A/2E antibody inhibition and 5-phenyl-pentyne lung experiments evidence_span: {"source_cache": "artifacts/coumarin-research/11950775.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861", "start_char": 0, "end_char": 1158, "text_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861"} [coumarin-p11950775] Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. (2002). https://pubmed.ncbi.nlm.nih.gov/11950775/ DOI: 10.1124/dmd.30.5.483

evidence_span

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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