Protective effects of curcumin, α-lipoic acid, and N-acetylcysteine against carbon tetrachloride-induced liver fibrosis in rats
Liver fibrosis is a major health problem that can lead to the development of liver cirrhosis and hepatocellular carcinoma. On the other hand, several antioxidants have been shown to possess protective effect against liver fibrosis. Therefore, in the present work, the effectiveness of curcumin, α-lipoic acid, and N-acetylcysteine in protecting against carbon tetrachloride (CCl4)-induced liver fibrosis as well as the mechanism(s) implicated in this protective effect was studied. The antioxidants used in this study resulted in hepatoprotective effect as evident by substantial decreases in collagen deposition in histopathological examinations in addition to significant decrease in serum levels of alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transpeptidase, bilirubin, and transforming growth factor-alpha (TGF-α) as well as hepatic malondialdehyde concentration, with a concurrent increase in serum matrix metalloproteinase-13 (MMP-13) and hepatic reduced glutathione (GSH) levels as compared to CCl4 fibrotic group. In conclusion, curcumin, α-lipoic acid, and N-acetylcysteine protect rats against CCl4-induced liver fibrosis most possibly through their antioxidant activities and their capacities to induce MMP-13 and to inhibit TGF-α levels.
KeywordsCurcumin α-Lipoic acid N-Acetylcysteine Liver fibrosis
- 7.Galicia-Moreno M, Rodríguez-Rivera A, Reyes-Gordillo K, Segovia J, Shibayama M, Tsutsumi V, Vergara P, Moreno MG, Muriel P (2009) N-Acetylcysteine prevents carbon tetrachloride-induced liver cirrhosis: role of liver transforming growth factor-beta and oxidative stress. Eur J Gastroenterol Hepatol 21:908–914PubMedCrossRefGoogle Scholar
- 8.Issa R, Zhou X, Trim N, Millward-Sadler H, Krane S, Benyon C, Iredale J (2003) Mutation in collagen-1 that confers resistance to the action of collagenase results in failure of recovery from CCl4-induced liver fibrosis, persistence of activated hepatic stellate cells, and diminished hepatocyte regeneration. FASEB J 17:47–49PubMedGoogle Scholar
- 11.Kato J, Sato Y, Inui N, Nakano Y, Takimoto R, Takada K, Kobune M, Kuroiwa G, Miyake S, Kohgo Y, Niitsu Y (2003) Ethanol induces transforming growth factor-alpha expression in hepatocytes, leading to stimulation of collagen synthesis by hepatic stellate cells. Alcohol Clin Exp Res 27:58S–63SPubMedCrossRefGoogle Scholar
- 20.Velasco-Loyden G, Pérez-Carreón JI, Agüero JF, Romero PC, Vidrio-Gómez S, Martínez-Pérez L, Yáñez-Maldonado L, Hernández-Muñoz R, Macías-Silva M, de Sánchez VC (2010) Prevention of in vitro hepatic stellate cells activation by the adenosine derivative compound IFC305. Biochem Pharmacol 80:1690–1699PubMedCrossRefGoogle Scholar