ABSTRACT
Alcohol and xenobiotics share the same metabolic microsomal pathway, which is mainly located in the endoplasmic reticulum of hepatocytes. This pathway involves enzymes that belong to the super family of cytochrome P450, and elucidates many pharmacokinetic or toxic interactions between alcohol and xenobiotics. Cytochrome P450 2E1 (CYP2E1) is the key enzyme of the microsomal pathway of ethanol oxidation. It is inducible by chronic ethanol consumption and its activity is increased three-to five-fold in liver from alcoholic subjects. This induction is also accompanied by enhanced activity of other enzymes resulting in accelerated metabolism of other drugs. Furthermore, CYP2E1 has a high capacity to activate numerous xenobiotics into toxic or carcinogenic compounds, often free radicals. These include common drugs such as paracetamol, anesthetics (enflurane, halothane), industrial solvents (benzene or its derivatives), halogenated solvents (carbon tetrachloride, trichlorethylene, chlorofluorocarbons), and N-nitrosamines which are present in food or tobacco smoke. Therefore, heavy consumption of alcohol, which results in CYP2E1 induction, increases individual susceptibility to the toxic or carcinogenic effects of these xenobiotics.
