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KMID : 0043320080310101317
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Archives of Pharmacal Research
2008 Volume.31 No. 10 p.1317 ~ p.1323
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Identification of Glutathione Conjugates of 1-Bromopentane and its Hepatotoxicity in Female BALB/c Mice
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Jeong Tae-Cheon
Kang Mi-Jeong
Yoo Hye-Hyun
Jeon Tae-Won
Seo Young-Min
Kim Ju-Hyun
Lee Dong-Ju
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Abstract
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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.
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KEYWORD
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1-Bromopentane, Glutathione, Conjugate structure, Hepatotoxicity, In vivo, Mice
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