Role of acetaldehyde in the pathogenesis of alcoholic liver disease.

Abstract

SummaryAcetaldehyde is the primary metabolic product of alcohol metabolism in the liver and is highly reactive. High concentrations may be achieved locally in the liver during alcohol abuse. Like alcohol, acetaldehyde appears not to be directly toxic to the liver cell but it binds non‐enzymatically to free amino groups in the proteins of the liver cell. The product of this addition reaction, the adduct, can alter the surface charge and structural conformation of protein molecules to expose new antigenic sites. The highly variable susceptibility to alcoholic liver disease is compatible with an immunologically mediated liver damage. The acetaldehyde adduct is also pro inflammatory in its own right and will activate the complement sequence, recruit and cause degranulation of neutrophils and stimulate neutrophil superoxide anion production. Acetaldehyde is also a substrate for free radical production in the liver. There is increasing evidence of both free radical and immunologically mediated damage in alcoholic liver disease. Although there is a increasing body of evidence to suggest that acetaldehyde is capable of inducing liver damage by such mechanisms, there is as yet no evidence to confirm that this actually occurs in alcohol abuse and the role of acetaldehyde remains speculative.