Acetaldehyde Adducts in Blood and Bone Marrow of Patients With Ethanol-Induced Erythrocyte Abnormalities

Jaana Latvala,Seppo Parkkila,Jukka Melkko,Onni Niemelä

doi:10.1007/bf03402186

Abstract

Although alcohol abuse is known to cause a wide array of adverse effects on blood cell formation, the molecular mechanisms by which alcohol exerts its toxic actions remain poorly defined. We examine here the formation of acetaldehyde-derived protein modifications in erythrocytes and in their bone marrow precursors using antibodies specifically recognizing acetaldehyde-modified epitopes in proteins independently of the nature of the carrier protein. We studied 138 consecutive adult patients undergoing bone marrow aspiration due to macrocytosis (MCV values above 99 fL). Assessment included complete blood counts, morphologic review, assessment of alcohol consumption, and biochemical and immunocytochemical assays for acetaldehyde adducts. There were 68 patients (49%) with a history of excessive alcohol consumption, 28 (20%) of whom were patients with severe dependence. The blood smears prepared from the alcoholic patients with macrocytosis also contained stomatocytes and knizocytes. Bone marrow aspirates from 12 alcoholic patients showed vacuolization of pronormoblasts and the presence of ring sideroblasts was noted in 8 cases. In immunocytochemical analyses of the peripheral blood erythrocytes, acetaldehyde-derived epitopes were found to occur both on the cell membrane and inside the erythrocytes. Bone marrow aspirates also showed positive staining for acetaldehyde adducts in the erythropoietic cells in 8 of 11 (73%) consecutive alcoholic patients. Separation of the erythrocyte proteins from the samples of alcoholics on HPLC-chromatography revealed the formation of fast-eluting hemoglobin fractions, which also reacted with antibodies against acetaldehyde adducts. Current data suggest that acetaldehyde-erythrocyte adducts are formed in vivo in blood and bone marrow of patients with excessive alcohol consumption. This may contribute to the generation of the erythrocyte abnormalities, which are frequently observed in alcoholic patients.

Highlights

Excessive ethanol intake is associated with a wide variety of morphologic abnormalities both in blood cells and in their bone marrow progenitors [1]
In a sample of 138 consecutive hospitalized patients or outpatients with macrocytosis undergoing bone marrow aspiration or biopsy, there were 68 patients (49%) with a history of excessive alcohol consumption, 28 of whom were patients with severe dependence
Bone marrow aspirates from the alcoholic patients showed excessive vacuolization of pronormoblasts in 12 patients, all of whom were patients with severe alcohol dependence and recent intoxication (Fig. 1)

Summary

Introduction

Excessive ethanol intake is associated with a wide variety of morphologic abnormalities both in blood cells and in their bone marrow progenitors [1]. Alcohol abuse is known to cause a wide array of adverse effects on blood cell formation, the molecular mechanisms by which alcohol exerts its toxic actions remain poorly defined. Bone marrow aspirates showed positive staining for acetaldehyde adducts in the erythropoietic cells in 8 of 11 (73%) consecutive alcoholic patients. Conclusions: Current data suggest that acetaldehydeerythrocyte adducts are formed in vivo in blood and bone marrow of patients with excessive alcohol consumption. This may contribute to the generation of the erythrocyte abnormalities, which are frequently observed in alcoholic patients

Methods

Results

Conclusion