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Archive > Volume 11 Issue 3 > 2019,11(3). DOI:10.1016/j.chmed.2019.07.001 Prev Next

Reviews

An important mechanism of herb-induced hepatotoxicity: To produce RMs based on active functional groups-containing ingredients from phytomedicine by binding CYP450s

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    Abstract:
    Reactive metabolites (RMs) generated by hepatic metabolism are thought to play an important role in the pathogenesis of drug-induced liver injury (DILI). Like many synthetic drugs undergoing metabolic activation to form RMs which are often associated with drug toxicity, it is recognized that some herbal components may be also converted to toxic, or even mutagenetic and carcinogenic metabolites by cytochrome P450s (CYP450s). This review focuses on the metabolic activation of herbal components and its liver toxicological implications. By summarizing references, we found that hepatotoxic herbal components via producing RMs have some certain structural dependence. There is a correlation between the generation of RMs and the structures, which provides a good chance for the early discovery of toxic ingredients in Traditional Chinese medicines (TCMs): i) A potential hepatotoxic component information database based on active functional groups can be built, which might provide an early information for the basic research of hepatotoxic substances in TCMs; ii) RMs can combine with CYP450s to form a complete antigen, which eventually leads to an antigen-specific immune response. RMs-CYP450 protein complete antigen can be set up, and the potential idiosyncratic liver toxicity might be predicted by testing RMs-CYP450 protein antibody in plasma.

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