INFLUENCE OF DIETARY LEVELS OF PROTEIN AND SULFUR AMINO-ACIDS ON THE FATE OF METHYLMERCURY IN MICE

We previously reported that the fate of methylmercury (MeHg) in mice w as affected by dietary protein levels. To study the mechanism of this alteration, we investigated the effect of sulfur amino acid supplement for a lowered protein diet on the fate of MeHg. C57BL/6N male mice we re fed on a 24.8% protein diet (normal protein diet, NPD), a 7.5% prot ein diet (low protein diet, LPD), or LPD supplemented by methionine an d cystine so as maintain the normal levels (amino acid supplemented di et, ASD) for 5 days. NPD-fed mice were used as controls. The mice were orally administered MeHg chloride (20 mu mol/kg), and were examined a fter 24 h distribution and excretion of Hg. The Hg level in brain incr eased with LPD feeding and was further enhanced by ASD feeding. The he patic Hg level increased only with ASD feeding. Although Hg levels in kidney, blood and plasma did not change with LPD feeding, these decrea sed with ASD feeding. The urinary Hg level that decreased with LPD fee ding was recovered and exceeded by far the control levels with ASD fee ding. When mice were intravenously injected with MeHg-bovine serum alb umin, the Hg uptake rate in the brain increased in LPD-fed mice and wa s further enhanced in ASD-fed mice. The brain uptake of intravenously injected L-[C-14]phenylalanine was also accelerated with LPD or ASD fe eding, which indicated that LPD or ASD feeding increased activity of n eutral amino acid transport in the brain. This would cause increased t ig uptake in the brain, since MeHg reaches the brain through this tran sport system. Hg ratio in plasma low molecular weight fraction increas ed in ASD-fed mice, but not in LPD-fed mice. This might contribute to the further enhanced Hg uptake in the brain with ASD feeding. Analysis of thiol compounds in plasma and urine revealed increased levels with ASD feeding. The present results suggest that insufficiency of sulfur amino acids in LPD is one reason for the alteration in the fate of Me Hg induced by LPD feeding. It is also suggested that the change in neu tral amino acid transport caused by LPD feeding is involved in the alt eration in the fate of MeHg.