Low-dose diethyldithiocarbamate attenuates the hepatotoxicity of 1,3-Dichloro-2-propanol and selectively inhibits CYP2E1 activity in the rat
Stott, Ian; Murthy, Anupama; Robinson, Alex; Thomas, Norman, W; Fry, Jeffrey, R; Stott, Ian, Department of Human Anatomy and Cell Biology, Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK; Murthy, Anupama, Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre; Robinson, Alex, Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre; Thomas, Norman, W, Department of Human Anatomy and Cell Biology, Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK; Fry, Jeffrey, R, Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre
Журнал:
Human and Experimental Toxicology
Дата:
1997
Аннотация:
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.
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