title: Identification of glutathione conjugates of 1-bromopentane and its hepatotoxicity in female BALB/c mice.
abstract: Halogenated organic compounds, such as 1-bromopentane (1-BPT), are used as cleaning agents, synthesis agents, or extraction solvents in the workplace. In the present study, glutathione (GSH) conjugation and hepatotoxicity induced by 1-BPT were investigated in female BALB/c mice. S-Bromopentyl GSH, S-bromopentyl cysteine, and mono-hydroxypentyl mercapturic acid were identified in liver by liquid chromatography-electrospray ionization tandem mass spectrometry. Oral treatment of mice with 1-BPT at 1500 mg/kg produced maximum GSH conjugates at 6 h after treatment. For hepatotoxicity tests, the animals were treated orally with 1-BPT at 375, 750, or 1500 mg/kg in corn oil once for a dose response study or at 1500 mg/kg for 6, 12, 24, or 48 h for a time course study. 1-BPT dose-dependently increased serum activity of ALT and AST and decreased hepatic GSH levels, peaking at 6 and 12 h after treatment. 1-BPT (750 and 1500 mg/kg) also significantly increased the hepatic content of malondialdehyde. Thus, 1-BPT could cause hepatotoxicity and depletion of GSH content by forming GSH conjugates, presenting a toxicity mechanism and potential biomarkers for low molecular weight haloalkanes.
authors.affiliation: Doping Control Center, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Sang Kyu
authors.initials: SK
authors.lastname: Lee
authors.forename: Dong Ju
authors.initials: DJ
authors.lastname: Lee
authors.forename: Hye Hyun
authors.initials: HH
authors.lastname: Yoo
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Young Min
authors.initials: YM
authors.lastname: Seo
authors.forename: Sil
authors.initials: S
authors.lastname: Shin
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Jeon
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Kang
authors.forename: Tae Cheon
authors.initials: TC
authors.lastname: Jeong
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000473:pathology*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D005978:Glutathione / Q000737:chemistry / Q000633:toxicity; D006842:Hydrocarbons, Brominated / Q000138:chemical synthesis* / Q000494:pharmacology*; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D006842:Hydrocarbons, Brominated; D008315:Malondialdehyde; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; C533538:1-bromopentane