Identification of glutathione conjugates of 1-bromopentane and its hepatotoxicity in female BALB/c mice

• Published in: Archives of pharmacal research Vol. 31; no. 10; pp. 1317 - 1323
• Main Authors: Lee, Sang Kyu, Lee, Dong Ju, Yoo, Hye Hyun, Kim, Ju Hyun, Seo, Young Min, Shin, Sil, Choi, Jae Ho, Jeon, Tae Won, Kang, Mi Jeong, Jeong, Tae Cheon
• Format: Journal Article
• Language: English
• Published: Heidelberg Pharmaceutical Society of Korea 01.10.2008; 대한약학회
• Subjects: alanine transaminase; Alanine Transaminase - blood; Animals; Aspartate Aminotransferases - blood; aspartate transaminase; biomarkers; blood serum; Body Weight - drug effects; Chemical and Drug Induced Liver Injury - enzymology; Chemical and Drug Induced Liver Injury - pathology; Chromatography, High Pressure Liquid; cleaning agents; corn oil; cysteine; dose response; Dose-Response Relationship, Drug; Female; females; glutathione; Glutathione - chemistry; Glutathione - toxicity; hepatotoxicity; Hydrocarbons, Brominated - chemical synthesis; Hydrocarbons, Brominated - pharmacology; ionization; liver; malondialdehyde; Malondialdehyde - metabolism; Medicine; Mice; Mice, Inbred BALB C; molecular weight; oral administration; Organ Size - drug effects; Oxidative Stress - drug effects; Pharmacology/Toxicology; Pharmacy; Research Article; solvents; Spectrometry, Mass, Electrospray Ionization; tandem mass spectrometry; working conditions; 약학; In vivo; Conjugate structure; Mice; 1-Bromopentane; Hepatotoxicity; Glutathione
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-001-2112-3

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.