Quercetin protects liver injury induced by bile duct ligation via attenuation of Rac1 and NADPH oxidase1 expression in rats

BACKGROUND:Bile duct ligation (BDL) and subsequent cholestasis are correlated with oxidative stress,hepatocellular injury and fibrosis.Quercetin is a flavonoid with antifibrotic,and hepatoprotective properties.However,the molecular mechanism underlying quercetin-mediated hepatoprotection is not fully understood.The current study was to evaluate mechanisms of hepatoprotective effect of quercetin in BDL rat model.METHODS:We divided male Wistar rats into 4 groups (n=8 for each):sham,sham+quercetin (30 mg/kg per day),BDL,and BDL+quercetin (30 mg/kg per day).Four weeks later,the rats were sacrificed,the blood was collected for liver enzyme measurements and liver for the measurement of Racl,Racl-GTP and NOX1 mRNA and protein levels by quantitative PCR and Western blotting,respectively.RESULTS:Quercetin significantly alleviated liver injury in BDL rats as evidenced by histology and reduced liver enzymes.Furthermore,the mRNA and protein expression of Racl,Racl-GTP and NOX1 were significantly increased in BDL rats compared with those in the sham group (P＜0.05);quercetin treatment reversed these variables back toward normal (P＜0.05).Another interesting finding was that the antioxidant markers e.g.superoxide dismutase and catalase were elevated in quercetin-treated BDL rats compared to BDL rats (P＜0.05).CONCLUSION:Quercetin demonstrated hepatoprotective activity against BDL-induced liver injury through increasing antioxidant capacity of the liver tissue,while preventing the production of Racl,Racl-GTP and NOX1 proteins.