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

Abstract

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 mg\\kg\\day atorvastatin); BDL group, and BDL+ At group (15 mg\\kg\\day 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.