Adachi T, Yasutake A, Hirayama K
Department of Basic Medical Sciences, National Institute for Minamata Disease, Kumamoto, Japan.
Toxicology. 1994 Nov 11;93(2-3):225-34. doi: 10.1016/0300-483x(94)90080-9.
We previously reported that the fate of methylmercury (MeHg) in mice was 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 were fed on 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 so as maintain the normal levels (amino acid supplemented diet, ASD) for 5 days. NPD-fed mice were used as controls. The mice were orally administered MeHg chloride (20 mumol/kg), and were examined after 24 h distribution and excretion of Hg. The Hg level in brain increased with LPD feeding and was further enhanced by ASD feeding. The hepatic Hg level increased only with ASD feeding. Although Hg levels in kidney, blood and plasma did not change with LPD feeding, these decreased with ASD feeding. The urinary Hg level that decreased with LPD feeding was recovered and exceeded by far the control levels with ASD feeding. When mice were intravenously injected with MeHg-bovine serum albumin, the Hg uptake rate in the brain increased in LPD-fed mice and was further enhanced in ASD-fed mice. The brain uptake of intravenously injected L-[14C]phenylalanine was also accelerated with LPD or ASD feeding, which indicated that LPD or ASD feeding increased activity of neutral amino acid transport in the brain. This would cause increased Hg uptake in the brain, since MeHg reaches the brain through this transport system. Hg ratio in plasma low molecular weight fraction increased 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 MeHg induced by LPD feeding. It is also suggested that the change in neutral amino acid transport caused by LPD feeding is involved in the alteration in the fate of MeHg.
我们之前报道过，小鼠体内甲基汞（MeHg）的代谢受饮食蛋白质水平的影响。为研究这种变化的机制，我们调查了在低蛋白饮食中补充硫氨基酸对MeHg代谢的影响。给C57BL/6N雄性小鼠喂食含24.8%蛋白质的饮食（正常蛋白质饮食，NPD）、含7.5%蛋白质的饮食（低蛋白饮食，LPD），或补充蛋氨酸和胱氨酸以维持正常水平的LPD（氨基酸补充饮食，ASD），持续5天。以喂食NPD的小鼠作为对照。给小鼠口服氯化甲基汞（20 μmol/kg），并在24小时后检测汞的分布和排泄情况。喂食LPD时脑中汞水平升高，而喂食ASD时进一步升高。肝脏汞水平仅在喂食ASD时升高。虽然喂食LPD时肾脏、血液和血浆中的汞水平没有变化，但喂食ASD时这些水平降低。喂食LPD时降低的尿汞水平在喂食ASD时恢复，且远远超过对照水平。当给小鼠静脉注射甲基汞 - 牛血清白蛋白时，喂食LPD的小鼠脑中汞摄取率增加，而喂食ASD的小鼠中进一步增加。喂食LPD或ASD也会加速静脉注射的L - [14C]苯丙氨酸在脑中的摄取，这表明喂食LPD或ASD会增加脑中中性氨基酸转运的活性。由于甲基汞通过该转运系统进入大脑，这会导致脑中汞摄取增加。喂食ASD的小鼠血浆低分子量部分中的汞比例增加，但喂食LPD的小鼠中未增加。这可能是喂食ASD时脑中汞摄取进一步增加的原因。血浆和尿液中硫醇化合物的分析显示，喂食ASD时其水平升高。目前的结果表明，LPD中硫氨基酸不足是LPD喂养引起MeHg代谢改变的一个原因。还表明，LPD喂养引起的中性氨基酸转运变化与MeHg代谢改变有关。
