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- W2956111931 abstract "Kavain is an active and major component in Piper methysticum Forst. (kava), which is a widely used dietary supplement for the treatment of anxiety, insomnia, and stress. However, kava-containing products can cause liver toxicity, and its underlying mechanisms are understudied. Cytochrome P450s (CYPs)-mediated bioactivation and biotransformation are highly associated with drug toxicity. In the current study, we profiled the metabolic pathways of kavain in mouse liver, urine, and feces. Overall, 28 kavain metabolites were identified including 17 new ones. The metabolic pathways of kavain include glutathione (GSH) conjugation, oxidation, dehydrogenation, O-demethylation, sulfation, and glucuronidation. The identification of kavain-GSH adducts suggests the formation of reactive metabolites of kavain in the liver. We further illustrated that CYP2C19, a highly polymorphic and inducible enzyme, was the major enzyme contributing to kavain biotransformation and bioactivation. Our data can be used to guide the safe use of kava products by preventing potential herb-drug interactions and hepatotoxicity." @default.
- W2956111931 created "2019-07-12" @default.
- W2956111931 creator A5003773524 @default.
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- W2956111931 date "2019-06-24" @default.
- W2956111931 modified "2023-09-24" @default.
- W2956111931 title "Enzymes and Pathways of Kavain Bioactivation and Biotransformation" @default.
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- W2956111931 doi "https://doi.org/10.1021/acs.chemrestox.9b00098" @default.
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