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

• Main Authors: Zohreh-al-sadat Ghoreshi, Razieh Kabirifar, Ameneh Khodarahmi, Alireza karimollah, Ali Moradi
• Format: Article
• Language: English
• Published: Mashhad University of Medical Sciences 2020-01-01
• Series: Iranian Journal of Basic Medical Sciences
• Subjects: atorvastatin; biliary duct-ligation; liver fibrosis; nox1; oxidative stress; rac1; rac1-gtp
• Online Access: http://ijbms.mums.ac.ir/article_14135_d0f7fa1ec15386a04f85b3932edf8c25.pdf

<em><strong>Objective(s):</strong></em> 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.<br /><em><strong>Materials and Methods:</strong></em> 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.<br /><em><strong>Results:</strong></em> 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). <br /><em><strong>Conclusion:</strong></em> 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.