title: Protective effect of acteoside on carbon tetrachloride-induced hepatotoxicity.
abstract: This study investigated the protective effects of acteoside, a phenylethanoid glycoside, on the carbon tetrachloride-induced hepatotoxicity as well as the possible mechanisms involved in this protection in mice. Pretreatment with acteoside prior to the administration of carbon tetrachloride significantly prevented the increased serum enzymatic activities of alanine and aspartate aminotransferase in a dose-dependent manner. In addition, pretreatment with acteoside significantly prevented the increase in hepatic malondialdehyde formation and the depletion of the reduced glutathione content in the liver of carbon tetrachloride-intoxicated mice. Carbon tetrachloride-induced hepatotoxicity was also essentially prevented, as indicated by a liver histopathologic study. The effects of acteoside on cytochrome P450 (P450) 2E1, the major isozyme involved in carbon tetrachloride bioactivation were also investigated. Treatment of the mice with acteoside resulted in a significant decrease in the P450 2E1-dependent pnitrophenol and aniline hydroxylation in a dose-dependent manner. Consistent with these observations, the P450 2El protein levels were also lower. Acteoside exhibited anti-oxidant effects on FeCl2-ascorbate induced lipid peroxidation in a mouse liver homogenate, and on superoxide radical scavenging activity. These results suggest that the protective effects of acteoside against the carbon tetrachloride-induced hepatotoxicity possibly involve mechanisms related to its ability to block the P450-mediated carbon tetrachloride bioactivation and free radical scavenging effects.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University, 375 Seosuk-dong, Kwangju 501-759, South Korea.
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Lee
authors.forename: Eun-Rhan
authors.initials: ER
authors.lastname: Woo
authors.forename: Chul Yung
authors.initials: CY
authors.lastname: Choi
authors.forename: Dong Weon
authors.initials: DW
authors.lastname: Shin
authors.forename: Dong Gun
authors.initials: DG
authors.lastname: Lee
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: You
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000097:blood; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D002712:Chlorides; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005960:Glucosides / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D015151:Immunoblotting; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D059808:Polyphenols
chemical_list: D000410:Alanine Transaminase; D000975:Antioxidants; D001205:Ascorbic Acid; D001219:Aspartate Aminotransferases; D002712:Chlorides; D019392:Cytochrome P-450 CYP2E1; D005290:Ferric Compounds; D016166:Free Radical Scavengers; D005960:Glucosides; D005978:Glutathione; D006899:Mixed Function Oxygenases; D010636:Phenols; D013481:Superoxides; C058956:acteoside; D059808:Polyphenols; C024555:ferric chloride