Covalent adducts of proteins with acetaldehyde in the liver as a result of acetaldehyde administration in drinking water

Background/Aims: Acetaldehyde, the first metabolic product of ethanol, has been suggested to be responsible for several adverse effects of ethanol through its ability to form covalent adducts with proteins and cellular constituents. It has recently been suggested that acetaldehyde derived from microbial ethanol oxidation in the gut could also contribute to the effects of ethanol in the liver. The present work aimed to examine whether modification of proteins by acetaldehyde occurs in rat liver as a result of acetaldehyde administration in drinking water. Methods: Rats were fed with either 0.7% acetaldehyde (n=10) or water (n=10) for 11 weeks. At the end of the feeding period, liver specimens were processed for immunohistochemistry for protein adducts with acetaldehyde and for hepatic cell type-specific protein markers. Results: Mild fatty change was found in the liver of the acetaldehyde-treated animals but not in the control animals. Immunohistochemical stainings for acetaldehyde adducts revealed intensive positive staining for acetaldehyde adducts in eight (80%) of the animals fed with acetaldehyde. The adducts were predominantly perivenular, although positive staining also occurred along the sinusoids and in the periportal area. Double immunofluorescence staining experiments revealed that hepatocytes were the primary targets of acetaldehyde adduct deposition, although stellate cells and Kupffer cells also showed weak positive reactions. Conclusions: The present data indicate that acetaldehyde-protein adducts are formed in the liver of animals following acetaldehyde administration in drinking water, which may contribute to the hepatotoxicity of extrahepatic acetaldehyde. These findings should be implicated in studies on the extrahepatic pathways of ethanol oxidation.