Puerarin improves ketoconazole-induced liver injury in rats by inhibiting aromatic hydrocarbon receptors/oxidative stress pathway
Objective This experiment aimed at exploring the mechanism ofprotective role of puerarin on ketoconazole-induced liver injury in rats.Method 48 male SD rats were randomly divided into control,model,low-dose and high-dose of puerarin-intervened groups(n=12 in each).Model was established by oral ketoconazole gavage,and intervention was carried out by oral ketoconazole and low-dose and large-dose of puerarin gavage simultaneously.Hepatic tissue aromatic hydrocarbon receptors(AHR),cytochrome P450 1A1(CYP1A1),and CYP2E1 mRNA levelswere assayed by RT-PCR,and hepatic expression of AHR protein was detected immunohistochemically.Results The model of liver injury was successfully established as proved enzymologically and histopathologically,and the intervention of puerarin greatly improved liver injury;hepatic tissue GSH level in low-dose puerarin-intervened group was(148.2±9.5)μM,much higher than[(77.0±9.1)µM,P＜0.05],while GSSG level was(84.7±9.3)µM,much lower than[(131.4±13.4)μM,P＜0.05]in the model,and in large-dose of puerarin intervention group,the changes were even more obviously;relative hepatic loads of AHR,CYP1A1 and CYP2E1 mRNA in low-dose of puerarin intervention were(28.4±3.3),(23.7±1.8)and(9.0±1.5),all significantly lower than[(51.7±7.8),(36.2±4.7)and(14.0±1.5),respectively,P＜0.05]in the model,and the changes were even more obvious in large-dose of puerarin intervention;AHR expression in liver tissues with puerarin intervention was obviously weaker as compared in the model.Conclusion Puerarin could ameliorate ketoconazole-induced liver injury in rats,which might be related to inhibition of oxidative stress pathway mediated by AHR.
万方数据
维普
