CCl[4] ilnduced 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 CCI[4] 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 CCI[4] or carnosine; group [II] CCI[4] group in which rats were subcutaneously injected with CCI[4] in a dose of 2 ml /Kg body weight twice weekly for 4 weeks; group[III] CCI[4] and carnosine group in which rats were also subcutaneously injected with CCI[4] 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 [PPARgammay] 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 CCI[4] 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 CCI[4-] induced hepatotoxicity due to its antioxidant properties