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 CCl₄ significantly prevented an increase in serum alanine, aspartate aminotransferase activity and hepatic lipid peroxidation in a dose-dependent manner. In addition, pretreatment with Naringin also significantly prevented the depletion of glutathione (GSH) content in the livers of CCl₄-induced mice. However, reduced hepatic glutathione levels was unaffected by treatment with Naringin alone. In addition, Naringin prevented CCl₄-induced apoptosis and necrosis, as indicated by a liver DNA laddering. To determine whether caspase-8, -3 pathway involved in CCl₄-induced acute liver injury, caspase-8, -3 activities were tested by ELISA. Naringin attenuated CCl₄-induced caspase-8, -3 activities in mouse livers. CCl₄-induced hepatotoxicity was also prevented, as indicated by a liver histopathologic study. The effects of Naringin on the cytochrome P450 (CYP) 2El, the major isozyme involved in CCl₄ were also investigated. Treatment of mice with Naringin resulted in a significant decrease of the CYP2El-dependent hydroxylation and aniline in a dose-dependent manner. These findings suggest that protective effects of Naringin against the CCl₄-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.
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