Ethanol interactions with other cytochrome P450 substrates including drugs, xenobiotics, and carcinogens

Chronic ethanol abuse is associated with increased activity of the microsom al ethanol-oxidizing system. This effect is due primarily to induction by e thanol of a specific cytochrome P450 (CYP2E1) responsible for enhanced oxid ation of ethanol and other P450 substrates and consequently, for metabolic tolerance to these substances. Furthermore, cytochrome 450 induction increa ses the activation of numerous xenobiotics to toxic metabolites and of chem ical carcinogens to reactive metabolites, thereby accelerating their advers e effects. Microsomal enzyme induction has been associated with increased r eactive oxygen species production and enhanced lipid peroxidation, as well as with decreased enzymatic and nonenzymatic scavenger activity, providing another possible explanation for ethanol-mediated toxicity. Yet another eff ect of chronic alcohol abuse is chronic immune system activation, which is the mechanism underlying alcohol-related liver disease. The metabolism of s teroids and vitamins is catalyzed by P350 and is altered in chronic alcohol ics. This article reviews recent advances in the understanding of ethanol i nteractions with drugs, toxic agents, and carcinogens, as well as with ster oids and vitamins.