Cytochromes P450 2A6 2E1, and 3A and production of protein-aldehyde adducts in the liver of patients with alcoholic and non-alcoholic liver diseases

Background/Aims: Interaction between CYP2E1, ethanol metabolites, and enhan ced lipid peroxidation is linked to the pathogenesis of alcoholic liver dis ease. This study was conducted to compare the expression of various cytochr ome enzymes and the appearance of aldehyde adducts in humans. Methods: Acetaldehyde- and lipid peroxidation-derived protein adducts and C YP2A6, 2E1, and 3A4/5 were examined immunohistochemically from liver specim ens of 12 alcohol abusers with either mild (n=7) or severe (n=5) liver dise ase, and from nine nondrinking patients with non-alcoholic steatosis (n=4), or hepatitis (n=5). Results: Ethanol-inducible CYP2E1 was present in all alcoholic livers. Whil e CYP2A6 in zone 3 hepatocytes was also abundant in the alcoholic patients with various degrees of liver disease, CYP3A4/5 was most prominent in alcoh olic cirrhosis, The sites of CYP2E1 and CYP2A6 immunoreactivity co-localize d with fatty deposits, and with the sites of acetaldehyde and lipid peroxid ation-derived protein adducts, The CYP enzymes were also abundant in the ce ntrilobular hepatocytes of patients,vith fatty liver due to obesity or diab etes. Conclusions: Alcohol-induced liver damage is associated with a generalized induction of CYP2A6, CYP2E1 and CYP3A4 and generation of acetaldehyde and l ipid peroxidation-derived protein-aldehyde adducts, However, CYP induction also occurred in patients with non-alcoholic steatosis.