Abstract: 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.

Key words: Drug-induced liver injury, Ketoconazole, Puerarin, Aromatic hydrocarbon receptors, Antioxidant, Rats