Inhibition of CYP2E1 with natural agents may be a feasible strategy for minimizing the hepatotoxicity of ethanol

CYP2E1, induced in hepatocytes by heavy consumption of ethanol and certain other drugs, is a potent generator of superoxide, and is thereby thought to mediate the gravest aspects of alcoholic hepatotoxicity. Certain drugs suc h as the sedative chlormethiazole are effective inhibitors of CYP2E1, and m ay have clinical potential in the treatment of alcoholics. A number of phyt ochemicals can also potently inhibit CYP2E1 - most notably certain isothioc yanates found in crucifera, such as sulforaphane and phenethylisothiocyanat e. Preparation of these compounds from crucifera seeds or sprouts should en able commercial production of supplements that would protect the livers of social drinkers while concurrently reducing risk for carcinogen-induced can cers. (C) 2001 Harcourt Publishers Ltd.