Ethanol induction of acetaminophen toxicity and metabolism

Chronic consumption of moderate amounts of ethanol (10% solution in the drinking water) dramatically enhances the toxicity of acetaminophen in CF-1 mice as demonstrated by a significant decrease in the LD₅₀. The increased toxicity appears to result from an acceleration in the microsomal biotransformation of acetaminophen to a reactive intermediate. Accelerated acetaminophen metabolism in ethanol-treated animals, in turn, causes more rapid depletion of glutathione. These studies suggest a mechanism to account for the toxic synergism between chronic alcohol consumption and acute acetaminophen intake.