Comparison of the formation of proteins modified by direct and indirect ethanol metabolites in the liver and blood of rats fed the Lieber-DeCarli liquid diet

It has been proposed that proteins modified by ethanol metabolites, such as acetaldehyde (AcH) or alpha-hydroxyethyl radicals (HER) may be an importan t step in the aetiology of alcoholic liver disease. Furthermore, it has als o been suggested that these modified proteins may act as a marker of ethano l intake. In this study, we have measured the generation of various types o f modified proteins in the liver and blood of ethanol-fed rats. Multiple ty pes of protein modification were observed in the livers of the ethanol-fed rats. In each case, the level of modification increased over the first 6 we eks of ethanol feeding, but reached a plateau by 10 weeks. In contrast to t he liver, elevated levels of proteins modified by malondialdehyde were not seen in the plasma of ethanol-fed animals, whereas elevated levels of modif ication due to AcH and HER were observed. In haemolysates from these animal s, only modification due to AcH was seen. Further investigation of the modi fication of plasma proteins showed that albumin, a protein produced in the liver, carried all the types of modification investigated, whereas immunogl obulin G, a protein derived from an extra-hepatic source, only carried modi fications due to acetaldehyde. This study demonstrates for the first time t hat modification of plasma proteins by ethanol metabolites can occur at bot h intra- and extra-hepatic sites.