OXIDATION OF CIRCULATING PROTEINS IN ALCOHOLICS - ROLE OF ACETALDEHYDE AND XANTHINE-OXIDASE

Background/Aims: This study aimed to evaluate the protein and lipid re dox status in plasma, erythrocytes and erythrocyte ghosts of alcoholic s and of patients with non-alcoholic liver disease; we also investigat ed the relation to glutathione levels and the role of acetaldehyde and xanthine oxidase activity in plasma. Methods: Carbonyl and sulfhydryl proteins, glutathione and malondialdehyde levels and the activity of the circulating xanthine oxidase were determined in: active and abstin ent alcoholics, patients with chronic viral hepatitis and healthy cont rols. Results: Active alcoholics showed a decrease of sulfhydryl prote in and glutathione concentrations in plasma, erythrocytes and ghosts c ompared to the other groups. Also, an increase of the carbonyl protein and malondialdehyde levels and of the activity of circulating xanthin e oxidase (9.2+/-1.8 nmol min ml, p<0.001) were observed. Significant correlations between carbonyl protein and malondialdehyde concentratio ns in plasma (r=0.775, p<0.001), as well as between daily alcohol inta ke and carbonyl protein content in plasma (r=0.879, p<0.001) and eryth rocytes (r=0.605, p<0.01) were observed. However, carbonyl protein lev els did not correlate with the degree of liver injury. Incubation of p lasma with acetaldehyde, but not with ethanol, significantly increased the carbonyl protein formation. Administration of N-Ethylmaleimide, a thiol depletor, or glutathione significantly increased or delayed, re spectively, the carbonyl protein formation. Conclusions: Proteins are oxidatively modified in plasma and erythrocytes of active alcoholics, whereas no such alterations are detectable in patients with non-alcoho lic liver disease. Protein oxidation in alcoholics does not seem to re sult directly from ethanol; circulating xanthine oxidase, delivered fr om injured cells, may play a contributory role and glutathione appears to be directly involved in the protection of plasma proteins against acetaldehyde toxicity.