title: Quercetin protects liver injury induced by bile duct ligation via attenuation of Rac1 and NADPH oxidase1 expression in rats.
abstract: 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<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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran. morady2008@gmail.com.
authors.forename: Razieh
authors.initials: R
authors.lastname: Kabirifar
authors.forename: Zohreh-Al-Sadat
authors.initials: ZA
authors.lastname: Ghoreshi
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Safari
authors.forename: Alireza
authors.initials: A
authors.lastname: Karimollah
authors.forename: Ali
authors.initials: A
authors.lastname: Moradi
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Eskandari-Nasab
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002779:Cholestasis / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D019610:Cytoprotection; D015536:Down-Regulation; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000201:enzymology / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000074624:NADPH Oxidase 1; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology*; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D000975:Antioxidants; D002374:Catalase; D024042:Collagen Type I; D006909:Hydroxyproline; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; D011794:Quercetin; D013438:Sulfhydryl Compounds; D013482:Superoxide Dismutase; D053773:Transforming Growth Factor beta1; D020830:rac1 GTP-Binding Protein; C508962:Tgfb1 protein, rat; C498862:Acta2 protein, rat; C000614712:NOX1 protein, rat; C499134:Rac1 protein, rat