Molecular hepatoprotective effects of lipoic acid against carbon tetrachloride-induced liver fibrosis in rats

Abstract

Background: Liver fibrosis is a noteworthy well-being issue that can prompt the progression of liver cirrhosis and hepatocellular carcinoma. Prominently, many antioxidants have been shown to have defensive impacts against liver fibrosis. Aim: Subsequently, in the present study, the viability of alpha-lipoic acid (α-LA) in ensuring against carbon tetrachloride (CCl4)-actuated liver fibrosis and the mechanism(s) involved in this defensive impact were considered in rats. Results: The present results uncovered that in the CCl4-treated group, the expression of antioxidant enzymes and matrix metalloproteinase-13 (MMP-13) messenger RNA (mRNA) was downregulated ( p < 0.05), and the levels of lipid peroxide and nitric oxide were increased ( p < 0.05) in the treated rat livers along with increased collagen deposition compared to that of the control group. Also, the gene expression levels of the proinflammatory factors interleukin-6 and tumor necrosis factor-alpha, nuclear factor-kappa B (NF-κB) p65, transforming growth factor-alpha, and inducible nitric oxide synthase (iNOS) were upregulated significantly ( p < 0.05) in the CCl4 group. These negative impacts were all restrained by α-LA. Conclusions: These outcomes show that α-LA might be compelling at forestalling collagen deposition and hepatic oxidative stress as well as downregulating the expression of hepatic proinflammatory cytokines, iNOS, and NF-κB and upregulating MMP-13 expression.