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Human & Experimental Toxicology
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Low-dose diethyldithiocarbamate attenuates the hepatotoxicity of 1,3-Dichloro-2-propanol and selectively inhibits CYP2E1 activity in the rat

Ian Stott

Department of Human Anatomy and Cell Biology, Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK

Anupama Murthy

Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre

Alex Robinson

Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre

Norman W Thomas

Department of Human Anatomy and Cell Biology, Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK

Jeffrey R Fry

Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre

The effect of low doses of diethyldithiocarbamate (DEDC) on hepatic cytochrome P450-dependent enzyme activity and 1,3-dichloro-2-propanol (DCP) hepatotoxicity in the rat have been investigated. DEDC at a dose of 5 mg/kg selectively inhibited enzyme markers for CYP2E1 activity, and provided substantial protection against DCP hepato toxicity. At a higher dose (25 mg/kg), DEDC also inhibited an enzyme marker for CYP1A2 activity and provided complete protection against DCP hepatotoxicity. It is concluded: (a) that DEDC at a dose of 5 mg/kg is a selective CYP2E1 inhibitor in the rat in vivo; and (b) that DCP hepatotoxicity is mediated principally by CYP2E1, with a possible contribution from CYP1A2.

Key Words: diethyldithiocarbamate • 1,3-Dichloropropanol • hepa totoxicity • rat • CYP2E1

Human & Experimental Toxicology, Vol. 16, No. 5, 262-266 (1997)
DOI: 10.1177/096032719701600505
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This article has been cited by other articles:


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[Abstract] [Full Text] [PDF]


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