Effect of d- or l-methionine and cysteine on the growth inhibitory effects of feeding 1% paracetamol to rats

Rats fed 1% paracetamol in the diet failed to grow and a dose-dependent inhibition of growth was observed and found to be independent of hepatotoxicity. Addition of 0.5% d- or l-methionine, or l-cysteine to a diet containing 1% paracetamol restored growth. Addition of l-methionine to the drinking water was equally effective. Feeding d-cysteine or sodium sulphate were ineffective. Acute paracetamol toxicity was also prevented by d- as well as by l-methionine. It is concluded that the inhibition of growth was due to depletion of sulphur amino acids in the course of paracetamol metabolism. This was sometimes followed by episodes of liver cell injury. Since the normal human dosage of paracetamol is up to 4 g/day, which is equivalent to 1% of the diet, the possibility of induction of amino acid deficiency by chronic use of paracetamol in normal dosage is raised.