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

• Published in: Hepatobiliary & pancreatic diseases international 2017-02, Vol.16 (1), p.88-95
• Main Authors: Kabirifar, Razieh, Ghoreshi, Zohreh-al-sadat, Safari, Fatemeh, Karimollah, Alireza, Moradi, Ali, Eskandari-nasab, Ebrahim
• Format: Article
• Language: English
• Subjects: Actins - genetics; Actins - metabolism; Animals; Antioxidants - pharmacology; Catalase - metabolism; Cholestasis - complications; Cholestasis - drug therapy; Cholestasis - enzymology; Cholestasis - pathology; Collagen Type I - genetics; Collagen Type I - metabolism; Cytoprotection; Down-Regulation; Endocrinology & Metabolism; Gastroenterology and Hepatology; Hydroxyproline - metabolism; Liver - drug effects; Liver - enzymology; Liver - pathology; Liver Cirrhosis, Experimental - enzymology; Liver Cirrhosis, Experimental - etiology; Liver Cirrhosis, Experimental - pathology; Liver Cirrhosis, Experimental - prevention & control; liver fibrosis; Male; NADH, NADPH Oxidoreductases - genetics; NADH, NADPH Oxidoreductases - metabolism; NADPH Oxidase 1; NOX1; oxidative stress; Oxidative Stress - drug effects; Protein Carbonylation - drug effects; quercetin; Quercetin - pharmacology; Rac1; rac1 GTP-Binding Protein - genetics; rac1 GTP-Binding Protein - metabolism; Rats, Wistar; Signal Transduction - drug effects; Sulfhydryl Compounds - metabolism; Superoxide Dismutase - metabolism; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism
• ISSN: 1499-3872
• DOI: 10.1016/S1499-3872(16)60164-9

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 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 Rac1, Rac1-GTP and NOX1 were significantly increased in BDL rats compared with those in the sham group ( P