CYP2E1 Level in Rat Liver Injured by the Interaction between Carbon Tetrachloride and Chloroform
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概要
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CYP2E1 Level in Rat Liver Injured by the Interaction between Carbon Tetrachloride and Chloroform : Hisayoshi IKATSU, et al. Center for Environmental Science and Technology, Okayama University-The toxic interaction between carbon tetrachloride (CCl_4) and chloroform (CHCl_3) was investigated in rats chronically pretreated with ethanol, and in rat liver microsomes. A combined exposure to 10 ppm CCl_4 and 50 ppm CHCl_3 increased plasma alanine aminotransferase (ALT) activity to a level similar to that by a single exposure to 50 ppm CCl_4. The single exposure decreased liver reduced glutathione (GSH) and cytochrome P450 (CYP) content, and N-nitrosodimethylamine N-demethylase (NDMAD) activity. The effects of combined exposure, however, were little or less than those of the single exposure. Immunoblot analysis with monoclonal antibody to CYP2E1 indicated that CYP2E1 was appreciably decreased after the single exposure but the enzyme remained after the combined exposure. The antibody inhibited CCl_4-induced lipid peroxidation in microsomes from ethanol-treated rats. Ethanol pretreatment increased the metabolic rate of CCl_4 and CCl_4-induced lipid peroxidation, but the coexistence of CHCl_3 and other hydrocarbons such as trichloroethylene and 1, 1, 1-trichloroethane did not increase the in vitro metabolic rate or the lipid peroxidation. The addition of GSH decreased CCl_4-induced lipid peroxidation, and the effect reached its maximum at 0.3 mM of GSH, so that the hepatotoxic interaction between CCl_4 and CHCl_3 at low dose exposure is more than additive when judged by the plasma ALT activity, but this is not true of the changes in drug-metabolizing enzyme activity and GSH depletion.
- 社団法人日本産業衛生学会の論文
著者
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Nakajima Tamie
Department Of Occupational And Environmental Health Nagoya University Graduate School Of Medicine
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井勝 久喜
吉備国際大学 政策マネジメント学部 環境リスクマネジメント学科
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井勝 久喜
岡山大学環境管理センター
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Shinoda Sumio
Department Of Environmental Hygiene Faculty Of Pharmaceutical Sciences Okayama University
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Ikatsu Hisayoshi
Center for Environmental Science and Technology, Okayama University
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Nakajima Tamie
Department Of Hygiene School Of Medicine Shinshu University
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