title: Pretreatment with 1,8-cineole potentiates thioacetamide-induced hepatotoxicity and immunosuppression.
abstract: The effect of 1,8-cineole on cytochrome P450 (CYP) expression was investigated in male Sprague Dawley rats and female BALB/c mice. When rats were treated orally with 200, 400 and 800 mg/kg of 1,8-cineole for 3 consecutive days, the liver microsomal activities of benzyloxyresorufin- and pentoxyresorufin-omicron-dealkylases and erythromycin N-demethylase were dose-dependently induced. The Western immunoblotting analyses clearly indicated the induction of CYP 2B1/2 and CYP 3A1/2 proteins by 1,8-cineole. At the doses employed, 1,8-cineole did not cause toxicity, including hepatotoxicity. Subsequently, 1,8-cineole was applied to study the role of metabolic activation in thioacetamide-induced hepatotoxicity and/or immunotoxicity in animal models. To investigate a possible role of metabolic activation by CYP enzymes in thioacetamide-induced hepatotoxicity, rats were pre-treated with 800 mg/kg of 1 ,8-cineole for 3 days, followed by a single intraperitoneal treatment with 50 and 100 mg/kg of thioacetamide in saline. 24 h later, thioacetamide-induced hepatotoxicity was significantly potentiated by the pretreatment with 1,8-cineole. When female BALB/c mice were pretreated with 800 mg/kg of 1,8-cineole for 3 days, followed by a single intraperitoneal treatment with 100 mg/kg of thioacetamide, the antibody response to sheep red blood cells was significantly potentiated. In addition, the liver microsomal activities of CYP 2B enzymes were significantly induced by 1,8-cineole as in rats. Taken together, our results indicated that 1,8-cineole might be a useful CYP modulator in investigating the possible role of metabolic activation in chemical-induced hepatotoxicity and immunotoxicity.
authors.affiliation: College of Pharmacy, Yeungnam University, Kyungsan 712-749, Korea.
authors.forename: Nam Hee
authors.initials: NH
authors.lastname: Kim
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Hyun
authors.forename: Chun Hua
authors.initials: CH
authors.lastname: Jin
authors.forename: Sang Kyu
authors.initials: SK
authors.lastname: Lee
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Lee
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Jeon
authors.forename: Jae Sung
authors.initials: JS
authors.lastname: Lee
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Chun
authors.forename: Eung Seok
authors.initials: ES
authors.lastname: Lee
authors.forename: Tae Cheon
authors.initials: TC
authors.lastname: Jeong
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000473:pathology*; D003511:Cyclohexanols / Q000494:pharmacology*; D004357:Drug Synergism; D004912:Erythrocytes / Q000276:immunology; D000077591:Eucalyptol; D007166:Immunosuppressive Agents / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008862:Microsomes, Liver / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D039821:Monoterpenes / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep / Q000276:immunology; D013853:Thioacetamide / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D003511:Cyclohexanols; D007166:Immunosuppressive Agents; D039821:Monoterpenes; D013853:Thioacetamide; D006899:Mixed Function Oxygenases; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000077591:Eucalyptol