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標題: Protective effects of fomepizole on 2-chloroethanol toxicity
作者: Chen, Y.T.
Liao, J.W.
Hung, D.Z.
關鍵字: 2-chloroethanol;chloroacetaldehyde;fomepizole;N-acetylcysteine;glutathione;liver alcohol-dehydrogenase;n-acetylcysteine;rat;metabolism;ifosfamide;4-methylpyrazole;chloroethanol;cytotoxicity;intoxication;glutathione
Project: Human & Experimental Toxicology
期刊/報告no:: Human & Experimental Toxicology, Volume 29, Issue 6, Page(s) 507-512.
2-Chloroethanol (2-CE) is a widely used industrial solvent. In Taiwan, Taiwanese farmers apply 2-CE on grapevines to accelerate grape growth, a practice that in some cases have caused poisoning in humans. Thus, there is strong interest in identifying antidotes to 2-CE. This study examines the protective role in 2-CE intoxicated rats. Alcohol dehydrogenase and glutathione were hypothesized to be important in the metabolism of 2-CE. This study used fomepizole, an alcohol dehydrogenase inhibitor, and chemicals that affected glutathione metabolism to study 2-CE toxicity. Notably, fomepizole 5 mg/kg significantly increased median lethal dose (LD(50)) of 2-CE from 65.1 to 180 mg/kg and reduced the production of a potential toxic metabolite chloroacetaldehyde (CAA) in animal plasma. In contrast, disulfiram (DSF), an aldehyde dehydrogenase inhibitor, increased the toxicity of 2-CE on the lethality in rats. Additional or pretreatment with N-acetylcysteine (NAC) and fomepizole significantly reduced plasma CAA concentrations. Fomepizole also significantly reduced 2-CE-inhibited glutathione activity. Otherwise, pretreatment with NAC for 4 days followed by co-treatment with fomepizole significantly decreased formation of the metabolic CAA. These results indicated that its catalytic enzyme might play a vital role during 2-CE intoxication, and the combination of fomepizole and NAC could be a protective role in cases of acute 2-CE intoxication.
ISSN: 0960-3271
DOI: 10.1177/0960327109358612
Appears in Collections:獸醫病理生物學所

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