The preventive effect of atorvastatin on liver fibrosis in the bile duct ligation rats via antioxidant activity and down-regulation of Rac1 and NOX1

Objective(s): Atorvastatin is a cholesterol-lowering agent capable of inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase. Recent studies have demonstrated new facets of atorvastatin, such as antioxidant and anti-fibrotic properties. We investigated the effect of atorvastatin on hepatic injury via the measurement of the antioxidant capacity and protein expression of NOX1, Rac1-GTP, and Rac1 in a rat biliary duct ligation (BDL) model.Materials and Methods: This study is regarded as experimental interventional research in which a total of 32 adult male Wistar rats (200-250 g) were assigned to 4 groups (eight rats per group) as follows: Control group; Control + At group (15 mgkgday atorvastatin); BDL group, and BDL+ At group (15 mgkgday atorvastatin). Expression levels of Rac1, NOX1, and Rac1-GTP were determined by western blot analysis. Besides, specific biomarkers of oxidative stress in hepatic tissues of all animals were also analyzed.Results: Atorvastatin reduced liver injury via a decrease in the expression of NOX1, Rac1-GTP, and Rac1 in the BDL group (P<0.05), while the increased contents of protein thiol groups were observed, and the protein carbonylation was decreased in atorvastatin-treated BDL rats compared to the BDL group (P<0.05). Also, administration of atorvastatin in the BDL group significantly lowered oxidative stress through increasing the activity of catalase and superoxide dismutase in comparison with the BDL group (P<0.05). Conclusion: It seems that atorvastatin has potential advantages in mitigation of liver fibrosis by a decrease in the expression of NOX1, Rac1-GTP, and Rac1, along with, a reduction in oxidative stress of liver tissues in rats induced by BDL. 

کلیدواژه های The preventive effect of atorvastatin on liver fibrosis in the bile duct ligation rats via antioxidant activity and down-regulation of Rac1 and NOX1:

Atorvastatin ، Biliary duct-ligation ، Liver fibrosis ، NOX1 ، Oxidative stress ، Rac1 ، Rac1-GTP