Effect of Alcohol Consumption and Acetaldehyde on Blood Cells and Molecules Pathogenic and Diagnostic Implications

Alcohol abuse is known to have a wide array of adverse effects on serum proteins, blood cells and their progenitors in bone marrow. The mechanisms by which it does so have not yet been established, however. Recent studies have suggested that acetaldehyde, the first metabolite of ethanol, is responsible for many of its harmful effects, being a highly reactive molecule and capable of forming stable condensates with proteins and cellular constituents. Acetaldehyde-derived protein condensates have also been suggested as possible new markers of alcohol abuse. The present work is focused on the effects of ethanol and acetaldehyde on blood cells and proteins. The formation of acetaldehyde-derived protein modifications in vivo was studied using antibodies recognizing acetaldehydemodified epitopes in proteins independently of the nature of the carrier protein. The subjects were patients representing a wide range of ethanol consumption and abnormalities in haematological parameters, alcoholics admitted for detoxification and patients with alcoholic liver disease. The controls were individuals without any history of excessive alcohol consumption. Routine haematological examinations of patients presenting with cytopenia and a history of hazardous drinking showed the incidence of anaemia to be lower than that in the corresponding non-alcoholic controls. Abnormal platelet and leukocyte levels were common, especially in the anaemic alcoholics. Both an elevated mean cell volume of erythrocytes (macrocytosis) (67% vs. 18%) and elevated mean cell haemoglobin (63% vs. 22%) were more frequent in the alcoholics. Reticulocytosis, thrombocytopenia and combined cytopenias were all common findings in the alcoholic patients. Blood smears from the alcoholics typically showed round macrocytes, stomatocytes and knizocytes. Bone marrow aspirates revealed vacuolization of pronormoblasts and megakaryocytes, especially in individuals with recent intoxication. Immunocytochemical analyses of peripheral blood erythrocytes indicated that acetaldehyde-derived epitopes occurred both on the cell membrane and inside the erythrocytes. Bone marrow aspirates also showed positive staining for acetaldehyde adducts in erythropoietic cells. Separation of erythrocyte proteins by high-pressure liquid chromatography revealed the formation of fast-eluting haemoglobin fractions which reacted with antibodies against acetaldehyde adducts.