Identification of glutathione conjugates of 1-bromopentane and its hepatotoxicity in female BALB/c mice.
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.
Lee
Sang Kyu
SK
Doping Control Center, Korea Institute of Science and Technology, Seoul, Korea.
Lee
Dong Ju
DJ
Yoo
Hye Hyun
HH
Kim
Ju Hyun
JH
Seo
Young Min
YM
Shin
Sil
S
Choi
Jae Ho
JH
Jeon
Tae Won
TW
Kang
Mi Jeong
MJ
Jeong
Tae Cheon
TC
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
D006842:Hydrocarbons, Brominated; D008315:Malondialdehyde; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; C533538:1-bromopentane