Disulfiram as a Tool in the Studies on the Metabolism of Acetaldehyde in Rats

AbstractThe liver acetaldehyde dehydrogenases and the acetaldehyde level in the blood during ethanol metabolism were studied in rats 24 hrs after the administration of disulfiram. High doses of disulfiram (150–600 mg/kg) caused a threefold decrease in the activity of the mitochondrial low‐Kmenzyme, whereas no significant effects were found on the activity of the high‐Kmenzymes present in the mitochondrial, the microsomal and the cytosolic fractions. The concentration of acetaldehyde was threefold higher in the hepatic venous blood and fivefold higher in the peripheral blood in rats given disulfiram compared to rats given ethanol only. Low doses of disulfiram (25–50 mg/kg) decreased the activity of the low‐Kmenzyme by 26 %, and caused a significant increase in the liver output of acetaldehyde. The rate of ethanol elimination decreased by 35 % at a high dose of disulfiram, whereas the alcohol dehydrogenase activity was not influenced. It is suggested that the mitochondrial low‐Kmenzyme has a primary role in the regulation of the hepatic output of acetaldehyde, and the results will be discussed with special reference to the site and kinetics of acetaldehyde oxidation during ethanol metabolism in rat liver.