Metabolic activities of cytochrome P-450 CYP2E1 and cytochrome P-450 CYP3A in hepatic alcohol-injuried rats

OBJECTIVE To study changes of metabolism activity of cytochrome P-450 CYP3A(CYP3A) and cytochrome P-450 CYP2E1(CYP2E1) in alcohol-mediated hepatic injury rats.METHODS An alcohol-injured hepatic injury model was established after rats were ig given alcohol.Activities of glutamyl pyruvic transaminase(GPT) and glutamyl oxaloacetic transaminase(GOT) in serum were determined,and the liver tissues were collected for histopathological assessment under the light microscrope.Rats were given ip CYP3A probe drug midazolam 10 mg·kg-1 or CYP2E1 probe drug chlorzoxazone 50 mg·kg-1.Concentrations of midazolam and chlorzoxazone in plasma were determined by HPLC,and their pharmacokinetic parameters were calculated by 3p87 software to evaluate metabolism activities of CYP3A and CYP2E1 indirectly.Rats were given ig chlorzoxazone 80 mg·kg-1.The analgesic effect was assayed by hot plate test.RESULTS Liver cells were severely damaged by alcohol,resulting in alcoholic hepatitis and the fat liver.Compared with normal control group,activities of GPT and GOT increased by 16.0% and 20.0%,respectively(P 0.05,P 0.01) ;metabolism activities of CYP3A and CYP2E1 were increased,AUC,t1/2 and cmax of chlorzoxazone decreased by 38.0%,30.5% and 35.0%(P 0.05) and those of midazolam decreased by 122.6%,54.9% and 56.9%(P 0.01,P 0.05).The analgesic effect significantly decreased in alcohol-induced hepatic injury group.CONCLUSION The CYP2E1 and CYP3A metabolism activity was reinforced in alcohol-induced hepatic injury rats.