Acetaldehyde/protein interactions: are they involved in the pathogenesis of alcoholic liver disease?

Alcohol abuse is a major cause of liver disease. While ethanol itself has been shown to be hepatotoxic, its primary metabolite acetaldehyde has also been implicated in the pathogenesis of alcoholic liver disease. The majority of ethanol metabolism occurs in the liver and high concentrations of acetaldehyde accumulate during chronic ethanol abuse. Acetaldehyde has been shown to react with many proteins in vitro, forming stable covalent adducts. These modifications can act as neoantigens and may also alter biological function. Acetaldehyde-modified proteins have been detected in the livers of ethanol-fed rats and human alcoholics. Circulating antibodies reactive with modified proteins have also been detected. A direct linkage between acetaldehyde-modified proteins, antibodies and liver damage has yet to be established, but current research should clarify the picture in the next few years.