AI Article Synopsis

  • - The study investigates the hepatotoxicity risks of physcion by examining its effects on bilirubin metabolism, focusing on the UGT1A1 enzyme involved in glucuronidation.
  • - Tests were conducted using rat liver microsomes to analyze how physcion impacts the UGT1A1 enzyme during both phase I and phase II metabolic reactions, showing varying levels of inhibition based on the reaction type.
  • - Results indicated that while physcion exhibited weak mixed inhibition when only phase II was initiated, stronger mixed inhibition occurred when both phases were activated, suggesting that physcion's metabolites could significantly contribute to liver toxicity.

Article Abstract

To evaluate the hepatotoxicity risks of physcion on the basis of the bilirubin metabolism mediated by glucuronidation of UDP-glucuronosyltransferases 1A1(UGT1A1 enzyme). The monomers were added into the rat liver microsomes to test the hepatotoxicity by using bilirubin as UGT1A1 enzyme substrate, with apparent inhibition constant K_i as the evaluation index. Liver microsome incubation in vitro was adopted to initiate phase Ⅱ metabolic reaction and investigate the inhibitory effect of physcion. Then the phase Ⅰ and Ⅱ metabolic reactions were initiated to investigate the comprehensive inhibition of metabolites and prototype components. The results showed that when only the phase Ⅱ reaction was initiated, physcion directly acted on the UGT1A1 enzyme in a prototype form, exhibited weak inhibition and the inhibition type was mixed inhibition; When the phase Ⅰ and Ⅱ reactions were initiated simultaneously, the inhibitory effects of physcion on UGT1A1 enzyme became strong and the inhibition type was mixed inhibition, suggesting that physcion had phase Ⅰ and Ⅱ metabolic processes, and the metabolites had strong inhibitory effect on UGT1A1 enzyme. This experiment preliminarily proved that the metabolites of physcion may be the main components to induce hepatotoxicity.

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http://dx.doi.org/10.19540/j.cnki.cjcmm.20190129.002DOI Listing

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