Protective effect of caffeic acid phenethyl ester against carbon tetrachloride-induced hepatotoxicity in mice

Abstract

This study was designed to investigate the protective effects of the phenethyl ester of caffeic acid (CAPE) against carbon tetrachoride (CCl 4)-induced hepatotoxicities in mice. Pretreatment with CAPE prior to administration of CCl 4 significantly prevented the increases in serum alanine, aspartate aminotransferase and alkaline phosphatase activities, hepatic lipid peroxidation formation, and depletion of glutathione content. In addition, CAPE prevented CCl 4-induced apoptosis and necrosis, as indicated by liver histopathology and DNA laddering studies. To determine whether the Fas/Fas ligand (FasL) pathway is involved in CCl 4-induced acute liver injury, Fas and FasL proteins and caspase-3 and -8 activities were tested by western blotting and ELISA. CAPE markedly decreased CCl 4-induced Fas/FasL protein expression levels and, in turn, attenuated CCl 4-induced caspase-3 and -8 activities in mouse liver. Moreover, the effect of CAPE on CYP2E1, the major isozyme involved in CCl 4 bioactivation, was investigated. Treatment with CAPE significantly decreased the CYP2E1-dependent hydroxylation of aniline. In addition, CAPE attenuated the CCl 4-mediated depletion of antioxidant enzyme (catalase, superoxide dismutase and glutathione- S-transferase) activities. These findings suggest that the protective effects of CAPE against CCl 4-induced acute liver injury may involve its ability to block CYP2El-mediated CCl 4 bioactivation and to protect against Fas/FasL-mediated apoptosis.