Significance of Acetaldehyde-Protein Adducts in Patients With Alcoholic Hepatitis

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Alcoholic hepatitis is characterized by acute inflammatory lesion of the liver caused by alcohol abuse, but the mechanism by which alcohol abuse induces hepatic inflammation is not known. Recently, the concept that chemically inert foreign substances are metabolically activated in the liver, combine with hepatic macromolecules and thereby cause liver injury has been invoked to explain the hepatotoxicity of a number of drugs. It is well-known that acetaldehyde is also an active metabolite of alcogol (ethanol) oxidation. Thus, acetaldehyde is possible to covalently bind to hepatocellular macromoecules and thereby alter hepatocellular structure and function. To test this, acetaldehyde (100uM) was perfused through the portal vein of SD rats for 60 min without recirculation and the formation of acetaldehyde adducts to isolated hepatocytes of the perfused rats was determined in vitro using tritiated sodium cyanoborohydride. The incorporation of the tritium was found to be detectable in the a … More cetaldehyde-treated hepatocytes. Then, to test an immunological reaction against the acetaldehyde-treated rat hepatocytes, sera from patients with alcoholic hepatitis were incubated with the isolated hepatocytes and serum antibodies to the adducts were determined. As a result, serum antibodies were found to be positive in 10 of 12 patients with alcoholic hepatitis, whereas they were negative in all 31 patients with non-alcoholic liver disease. In order to study cytotoxic T-cell response to acetaldehyde adducts, lymphocytes taken from patients with alcoholic and non-alcoholic liver diseases were incubated with acetaldehyde, and one part was used as stimulator cells and another as target cells after labeled with Cr. When lymphocytes activated with the stimulator cells were cultured with the target cells, lymphocyte cytotoxicity was detected in 5 of 18 patients with alcoholic liver disease. The cytotoxicity was not found in 14 patients with non-alcoholic liver disease. All these results suggest that lymphocytotoxic response to acetaldehyde-protein adducts is, at least in part, play a role for the inflammatory reaction caused by alcohol abuse. Less