Influence of Dietary Levels of Protein and Sulfur Amino Acids on the Subacute Toxicity of Methylmercury in Mice

Abstract

The influence of diet on the subacute toxicity of methylmercury (MeHg) was investigated using C57BL/6N male mice, each fed a 24.8% protein diet (normal protein diet, NPD), a 7.5% protein diet (low protein diet, LPD) or LPD supplemented by methionine and cystine to NPD level (amino acid supplemented diet, ASD). When MeHg was consecutively administered to each group of mice (20 µmol/kg per day), median survival times were 11, 18 and 30 d in ASD-, LPD- and NPD-fed mice, respectively. Toxic symptoms including ataxia and loss of body weight were in that order. Hg accumulation rate in brain was faster in LPD-fed mice than in NPD-fed mice, and was further enhanced in ASD-fed mice. The fact that Hg in plasma low molecular weight (LMW) fraction was in the order of ASD-> LPD-> NPD-fed mice, would be one reason for the difference in the brain Hg accumulation. Hg levels in liver, blood and plasma showed a monotonous increase, and their terminal Hg levels were similar in the three groups. Renal Hg levels increased rapidly and almost never changed from the 7th d in the three groups. Urinary excretion of Hg in LPD-fed mice was markedly lower than in NPD-fed mice throughout the experimental period; that in ASD-fed mice, which was the highest at least for the first few days, began to decline earliest. No difference was observed in fecal Hg levels during the early part of the experiment. Our results suggest that diet is an important factor determining the susceptibility to subacute MeHg toxicity, and that accelerated Hg accumulation rate in the brain caused by diet would result in higher susceptibility to subacute MeHg toxicity. © 1995, The Pharmaceutical Society of Japan. All rights reserved.