CCl4-Induced Hepatotoxicity: Protective Effects of Carnosine on Peroxisome Proliferator-Activated Receptor Gamma Gene Expression, Genotoxicity and Oxidant/Antioxidant Status in Rats

Abstract

Effect of carnosine as an antioxidant in protection against carbon tetrachloride (CCl₄) induced oxidative stress and hepatotoxicity in rats was investigated. Liver toxicity was induced in rat model at which four experimental groups of 20 rats each were constructed: group (1) the control group in which rats were not administrated CCl₄ or carnosine; group (II) CCl₄ group in which rats were subcutaneously injected with CCl₄ in a dose of 2 ml /Kg body weight twice weekly for 4 weeks; group (III) CCl₄ and carnosine group in which rats were also subcutaneously injected with CCl₄ and co-treated with daily intraperitoneal (i.p.) carnosine at a dose of 10 mg / kg body weight and group (IV) received also i.p. repeated daily dose of carnosine. Hepatotoxicity was assessed by measurement of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. Hepatic peroxisome proliferator-activated receptor gamma (PPARy) mRNA expression, glutathione-S-transferase (GST) activity, paraoxonase 1 (PON1) activity, xantheine oxidase (XO) activity and total anti-oxidant capacity (TAC) level as well as DNA damage in blood were evaluated. The results were confirmed by histopathological examination. Carnosine treatment significantly prevented the CCl₄- induced hepatotoxicity, oxidative stress and DNA damage. In conclusion, our results suggested that carnosine might be a therapeutic antifibrotic/antigenotoxic agent for the treatment of CCl₄-induced hepatotoxicity due to its antioxidant properties.

Keywords: Carbon tetrachloride; Hepatotoxicity; Oxidative stress; Carnosine; Peroxisome proliferator-activated receptor gamma