title: Role of flavin-containing-monooxygenase-dependent neutrophil activation in thioacetamide-induced hepatic inflammation in rats.
abstract: Thioacetamide is widely used in industry and is known to be one of the most potent hepatotoxicants in experimental animals. We investigated the involvement of flavin-containing monooxygenase (FMO)-dependent hepatic-neutrophil activation and the release of proinflammatory mediators in thioacetamide-induced hepatic injury in rats. Thioacetamide (100 mg/kg, intraperitoneally) increased, within 12 h, hepatic serum aspartate transferase and alanine transferase levels, tumor necrosis factor-α production, interleukin-1β and nitrite levels, and myeloperoxidase activity. Rabbit anti-neutrophil serum markedly inhibited all thioacetamide-altered parameters. In addition, FMO-competitive inhibitor methimazole reduced thioacetamide-induced myeloperoxidase activity, hepatic tumor necrosis factor-α, interleukin-1β, nitrite, inducible nitric oxide synthase, and hepatic damage in thioacetamide-treated rats. Thus, we conclude that FMO-dependent hepatic neutrophil activation initiates the release of proinflammatory mediators in thioacetamide-treated rats.
authors.affiliation: Department of Environmental and Occupational Health, National Cheng Kung University Medical College, National Cheng Kung University, Tainan 70428, Taiwan. durzonghsu@gmail.com
authors.forename: Dur-Zong
authors.initials: DZ
authors.lastname: Hsu
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Chu
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Li
authors.forename: Victor Raj Mohan
authors.initials: VR
authors.lastname: Chandrasekaran
authors.forename: Ming-Yie
authors.initials: MY
authors.lastname: Liu
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006505:Hepatitis / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects* / Q000502:physiology*; D010105:Oxygenases / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide / Q000633:toxicity*
chemical_list: D013853:Thioacetamide; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)