4.3 Article

Molecular hepatoprotective effects of lipoic acid against carbon tetrachloride-induced liver fibrosis in rats: Hepatoprotection at molecular level

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HUMAN & EXPERIMENTAL TOXICOLOGY
卷 37, 期 2, 页码 142-154

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SAGE PUBLICATIONS LTD
DOI: 10.1177/0960327117693066

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Lipoic acid; liver fibrosis; nuclear factor-kappa B; transforming growth factor-alpha; matrix metalloproteinase-13; inducible nitric oxide synthase

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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 (-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-B) 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 -LA. Conclusions: These outcomes show that -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-B and upregulating MMP-13 expression.

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