出版社：Korean Society of Environmental Health and Toxicology
摘要：The protective effects of the Naringin,on carbon tetrachloride (CCl4)-induced hepatotoxicity and the possible mechanisms involved in this protection were investigated in mice. Pretreatment with Naringin prior to the administration of CCI4 significantly prevented an increase in serum alanine,aspartate aminotransferase acti- vity and hepatic lipid peroxidation in a dose -dependent manner. In addition,pretreatment with Naringin also signi- ficantly prevented the depletion of glutathione (GSH) content in the livers of CCl-induced mice. However, reduced hepatic glutathione levels was unaffcted by treatment with Naringin alone. In addition,Naringin pre- vented CCl-induced apoptosis and necrosis,as indicated by a liver DNA laddering. To determine whether cas- pase-8,-3 pathway involved in CCl-induced acute liver injury,caspase-8,-3 activities were tested by ELISA. Naringin attenuated CCl4 induced caspase-8,-3 activities in mouse livers. CCl-induced hepatotoxicity was also prevented,as indicated by a liver histopathologic study. The efects of Naringin on the cytochrome P450 (CYP) 2E1,the major isozyme involved in CCl4 were also investigated. Treatment of mice with Naringin resulted in a significant decrease of the CY P2E1-dependent hydroxylation and aniline in a dose -dependent manner. These findings suggest that protective efets of Naringin against the CCl-induced hepatotoxicity may be due to its ability to block CYP2El-mediated CCl4 bioactivation and that is also protects against caspase-8,-3 pathway mediated apoptosis.
