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 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 (PConclusion: 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.

Keywords

• atorvastatin
• biliary duct-ligation
• liver fibrosis
• nox1
• oxidative stress
• rac1
• rac1-gtp