Effects of Shenmai injection on the activity of hepatic microsomal CYP450 iszymes in rats

Objective: To investigate the influence of Shenmai injection(SMI) on the activity and mRNA expression of cytochrome P450(CYP450) system in rat liver microsomes.Methods: Rat liver microsomes were prepared after a fourteen-day continuous administration of SMI.An HPLC-MS method was applied to determine the metabolites formation of six CYP450 probe substrates(phenacetin for CYP1A2,tolbutamide for CYP2C9,bupropion for CYP2B6 and midazolam for CYP3A) in rat liver microsomal incubations.The activity of CYP450 isozymes were represented by the formation of metabolites.A RT-PCR method was applied to determine the mRNA expression levels of CYP450.Results: SMI significantly induced the activity of CYP2B6 and CYP2C9(P 0.05),but did not affect those of CYP1A2 and CYP3A.HSI significantly induced the activity of CYP1A2,CYP2B6 and CYP2C9(P 0.05),and had an inhibition trend on the activity of CYP3A(not statistically different from control).MDI induced the activity of CYP2C9(P 0.05).At the mRNA level,SMI induced the expression of CYP1A2,CYP2B and CYP2C,while HSI and MDI induced the expression of CYP2C.HSI had an inhibition trend on the expression of CYP3A,but did not statistically differ from control.Conclusion: The possibility of interaction between SMI and coadministrative drugs will be considered base on the levels and subtypes of CYP450 involved in the drug metabolism.