Hepatoprotective effect of astaxanthin against cholestasis liver fibrosis induced by bile duct ligation in adult Wistar rats

Abstract

In this study, we evaluated the hepatoprotective effects of astaxanthin, a natural carotenoid, against the cholestatic liver fibrosis induced by bile duct ligation (BDL). Toward this end, male rats were subjected to BDL and treated with astaxanthin for 35 days. Afterwards, their serum and liver biochemical factors were assessed. Also, histopathological and immunohistochemical analyses were performed to determine the fibrosis and the expression levels of alpha-smooth muscle actin (alpha-SMA) and transforming growth factor beta (TGF-ss 1) in the liver tissue. Based on the results, BDL caused a significant increase in liver enzyme levels, blood lipids, and bilirubin, while decreasing the activity of superoxide dismutase(SOD), catalase (CAT), and glutathione (GSH) enzymes. Also, in the BDL rats, hepatocyte necrosis, infiltration of inflammatory lymphocytes, and hyperplasia of bile ducts were detected, along with a significant increase in alpha-SMA and TGF-ss 1 expression. Astaxanthin, however, significantly prevented the BDL's detrimental effects. In all, 10 mg/kg of this drug maintained the bilirubin and cholesterol serum levels of BDL rats at normal levels. It also reduced the liver enzymes' activity and serum lipids, while increasing the SOD, CAT, and GSH activity in BDL rats. The expression of alpha-SMA and TGF-ss 1 in the BDL rats treated with 10 mg/kg of astaxanthin was moderate (in 34-66 of cells) and no considerable cholestatic fibrosis was observed in this group. However, administrating the 20 mg/kg of astaxanthin was not effective in this regard. These findings showed that astaxanthin could considerably protect the liver from cholestatic damage by improving the biochemical features and regulating the expression of related proteins. A set of anomalies in the liver tissue of animals subjected to bile duct ligation (BDL) include necrotic hepatocytes, infiltration of inflammatory cells (lymphocytes), bile ducts hyperplasia, infiltration of connective tissue between necrotic and regenerated hepatocytes, and creation of incomplete liver lobules. Receiving 10 mg/kg of astaxanthin (AST10) significantly reduced these abnormalities. image