Study on hepatotoxicity of physcion based on liver metabolism in vitro.
10.19540/j.cnki.cjcmm.20190129.002
- Author:
Qi WANG
1
;
Ya-Dan WANG
1
;
Jian-Bo YANG
1
;
Yue LIU
1
;
Hai-Ruo WEN
1
;
Shuang-Cheng MA
1
Author Information
1. National Institutes for Food and Drug Control Beijing 100050, China.
- Publication Type:Journal Article
- Keywords:
UGT1A1 enzyme;
metabolite;
phase Ⅰ metabolism;
phase Ⅱ metabolism;
physcion
- MeSH:
Animals;
Chemical and Drug Induced Liver Injury;
Emodin;
analogs & derivatives;
toxicity;
Glucuronosyltransferase;
metabolism;
Kinetics;
Microsomes, Liver;
drug effects;
Rats
- From:
China Journal of Chinese Materia Medica
2019;44(11):2367-2372
- CountryChina
- Language:Chinese
-
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.
