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Prolonged Acetaminophen Ingestion in Mice: Effects on the Availability of Methionine for Metabolic Functions^1,2,

Division of Nutrition, HFF-268, Food and Drug Administration, Washington, D.C. 20204

The objective of this study was to determine the effect of prolonged ingestion of acetaminophen (ACAP) on the availability of methionine for its metabolic functions in mice. ACAP was fed to weanling mice at levels of 0.0, 0.3, 0.5 or 0.8% of the diet, with methionine provided at requirement (0.5%) or at twice the requirement (1.0%) level, for 2 wk to assess its effect on the availability of methionine for growth. In another study, ACAP was fed to adult mice at levels of 0.0, 0.4, or 0.6% of the diet, with methionine at 0.5 or 1.0% of the diet, for 2 wk to assess its effect on the availability of methionine for protein synthesis and methylation reactions. The growth rate of weanling mice decreased with increasing dietary ACAP in mice fed 0.5% methionine, but not in those fed 1.0%. Hepatic reduced glutathione (GSH) decreased and plasma glutamic-pyruvic transaminase activity increased in an ACAP dose-dependent manner in weanling mice fed 0.5% methionine. Protein synthesizing ability decreased in adult mice fed 0.5% methionine and 0.6% ACAP. Relative liver weight and liver lipid decreased with increasing dietary ACAP in mice fed methionine at or above requirement. Neither plasma creatinine or muscle creatine was affected by variations in dietary methionine or ACAP. Ingestion of ACAP for a prolonged period of time increased the methionine requirement for growth, maintenance of hepatic GSH level and protein synthesis, but did not affect the methionine requirement for methylation reactions.

KEY WORDS: • acetaminophen • methionine • mice • glutathione • N-methylnicotinamide • glutamic-oxaloacetic transaminase • glutamic-pyruvic transaminase • plasma creatinine • liver lipids • muscle creatine • protein synthesis

¹ Presented in part at the 72nd Annual Meeting of the Federation of American Societies for Experimental Biology, Las Vegas, NV, May 1988 [Reicks, M. and Hathcock, J. N. (1988) Effect of prolonged acetaminophen ingestion on the methionine growth requirement in weanling mice. Fed. Proc. 2: A1573 (abs. 7418)].

² The studies reported herein were conducted according to the principles set forth in the Guide for the Care and Use of Laboratory Animals, Institute of Laboratory Animal Resources, National Research Council, NIH Pub. 1986, No. 86-23.

Manuscript received 3 February 1989. Revision accepted 3 April 1989.