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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 Rac1, Rac1-GTP and NOX1 mR NA 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 m RNA and protein expression of Rac1,Rac1-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 Rac1, Rac1-GTP and NOX1 proteins.
BACKGROUND: Bile duct ligation (BDL) and subsequent cholestasis are correlated with oxidative stress, hepatocellular injury and fibrosis. 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 Rac1, Rac1-GTP and NOX1 mR NA 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. Frthermore, the m RNA and protein expression of Rac1, Rac1-GTP and NOX1 were significantly increased in BDL rats compared with those in the sham group (P <0.05); quercetin-activated vectors reversed these normal (P <0.05). Another interesting finding was that the antioxidant markers eg 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 Rac1, Rac1-GTP and NOX1 proteins.