Protective effect of caffeic acid phenethyl ester against carbon tetrachloride-induced hepatotoxicity in mice.
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.
Lee
Kyung Jin
KJ
BK21 Project Team, Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University, Gwangju, South Korea.
Choi
Jae Ho
JH
Khanal
Tilak
T
Hwang
Yong Pil
YP
Chung
Young Chul
YC
Jeong
Hye Gwang
HG
D000818:Animals; D002109:Caffeic Acids / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology*; D012997:Solvents / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D002109:Caffeic Acids; D053222:Fas Ligand Protein; C491899:Fas protein, mouse; D020011:Protective Agents; D012997:Solvents; D019014:fas Receptor; D002251:Carbon Tetrachloride; D002374:Catalase; D019392:Cytochrome P-450 CYP2E1; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D053148:Caspase 3; D053181:Caspase 8; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol