The effect of diet on the toxicity of paracetamol and the safety of paracetamol-methionine mixtures

Abstract

Rats fed low protein or 25% yeast diets are highly susceptible to the lethal and hepatotoxic effects of oral paracetamol ( N-acetyl- p-aminophenol, acetaminophen). Phenobarbitone pre-treatment makes the protein-depleted animals even more sensitive. The liver injury produced is patchy in distribution and is best measured by relating plasma enzyme activity to the area of liver involved. Glutathione levels in the liver fall similarly after yeast and 3% casein + phenobarbitone diets, but the yeast fed animals are more sensitive to paracetamol, in spite of lower cytochrome P-450 levels. Addition of methionine to the oral paracetamol dose protects against death and liver injury, and it is suggested that this may be a useful technique for making paracetamol safe against the danger of overdose.