Effects Of Three Inducers On CYP2E1 Expression And Liver - Related Enzymes In Rats

The main function of CYP2E1is the metabolism of small-molecular compounds. The research onCYP2E1has important significance in drug toxicology，as many substrates for CYP2E1are before the poisonor procarcinogen and could have a toxicological effects after the metabolize of CYP2E1.In this study,imidazole, pyrazole and acetaminophen are different types of small-molecular compound of CYP2E1substrates, and could affect the expression and enzyme’s activity of CYP2E1according to research reported.The three compounds were selected to investigate their effect on the regulation of CYP2E1expression andliver injury within24hours in this experiment.180SD rats were randomly divided into three batches imidazole, acetaminophen, pyrazole were inducedin rats. Imidazole60rats were divided into control group and low, medium and high concentration of druggroups of15, after intraperitoneal injection, respectively, in1h,6h and24h,5rats in each group wererandomly selected, blood collection and separation of the liver at-80℃stored for use. acetaminophen andpyrazole are same as imidazole groups.The expression level of CYP2E1mRNA in liver of rats weredetermined by qRT-PCR. The expression level of CYP2E1protein was determined by Western Blot method.The enzyme activity assay of CYP2E1was detected by ultraviolet spectrophotometer method. The levels of6kinds of enzyme changed in plasma or liver were detected by the colorimetric method.The results showed that three kinds of drugs had no significant effect on the expression level of CYP2E1mRNA (P>0.05).Compared with the control group, CYP2E1protein and enzyme activity on point in time of1h and6h administration had no significant changes in imidazole group with different dose-dependent. Andincreased on point in time of24h and showed dose-dependent; Protein and enzyme activity on point in timeof1h and6h were significantly higher than control group（P<0.05), and returned to normal on point in time of24h;The expression of protein showed dose-dependent and time of administration-dependent, and enzymeactivity was significantly increased on point in time of24h after administration. All of the three drugs couldinordinately increase the levels of AST, ALT and ALP in plasma and MDA in liver, and inordinatelydecreased the levels of GSH and SOD in liver.In summary, within24hours, effects of imidazole, pyrazole and acetaminophen on CYP2E1inductionmainly through the influence of CYP2E1protein expression quantity and enzyme activity, instead of theCYP2E1mRNA expression. But the effects of various drugs on the protein expression of CYP2E1and theactivity of the enzyme in the liver of rats were different from the time. The high dose of a imidazole andpyrazole on point time of24h could lcause liver of rats injuring slightly,acetaminophen was showed dose-dependent and time of administration-dependent on degree of liver injure.