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Hum Exp Toxicol. 2018 Feb;37(2):142-154. doi: 10.1177/0960327117693066. Epub 2017 Feb 21.

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

Author information

1
1 Department of Biochemistry, Faculty of Veterinary Medicine, Damanhur University, Damanhur, Egypt.
2
2 Department of Food Hygiene, Faculty of Veterinary Medicine, Damanhur University, Damanhur, Egypt.
3
3 Department of Molecular Biology and Genetics, Faculty of Veterinary Medicine, Damanhur University, Damanhur, Egypt.

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.

KEYWORDS:

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

PMID:
29233029
DOI:
10.1177/0960327117693066
[Indexed for MEDLINE]

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