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Abstract Title:

Curcumin protects against acute liver damage in the rat by inhibiting NF-kappaB, proinflammatory cytokines production and oxidative stress.

Abstract Source:

Biochim Biophys Acta. 2007 Jun;1770(6):989-96. Epub 2007 Feb 22. PMID: 17383825

Abstract Author(s):

Karina Reyes-Gordillo, José Segovia, Mineko Shibayama, Paula Vergara, Mario G Moreno, Pablo Muriel

Article Affiliation:

Sección Externa de Farmacología, Cinvestav-IPN., Apdo. Postal 14-740. México 07000, D.F. Mexico.

Abstract:

Curcumin, an anti-inflammatory and antioxidant compound, was evaluated for its ability to suppress acute carbon tetrachloride-induced liver damage. Acute hepatotoxicity was induced by oral administration of CCl4 (4 g/kg, p.o.). Curcumin treatment (200 mg/kg, p.o.) was given before and 2 h after CCl4 administration. Indicators of necrosis (alanine aminotransferase) and cholestasis (gamma-glutamyl transpeptidase and bilirubins) resulted in significant increases after CCl4 intoxication, but these effects were prevented by curcumin treatment. As an indicator of oxidative stress, GSH was oxidized and the GSH/GSSG ratio decreased significantly by CCl4, but was preserved within normal values by curcumin. In addition to its antioxidants properties, curcumin is capable of preventing NF-kappaB activation and therefore to prevent the secretion of proinflammatory cytokines. Therefore, in this study we determined the concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) mRNA, and NF-kappaB activation. CCl4-administered rats depicted significant increases in TNF-alpha, IL-1beta, and IL-6 production, while curcumin remarkably suppressed these mediators of inflammation in liver damage. These results were confirmed by measuring TNF-alpha, and IL-1beta protein production using Western Blot analysis. Accordingly, these proteins were increased by CCl4 and this effect was abolished by curcumin. Administration of CCl4 induced the translocation of NF-kappaB to the nucleus; CCl4 induced NF-kappaB DNA binding activity was blocked by curcumin treatment. These findings suggest that curcumin prevents acute liver damage by at least two mechanisms: acting as an antioxidant and by inhibiting NF-kappaB activation and thus production of proinflammatory cytokines.

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Sayer Ji
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