Zalups R K, Barfuss D W
Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, Georgia 31207, USA.
J Toxicol Environ Health. 1995 Apr;44(4):385-99. doi: 10.1080/15287399509531968.
The accumulation and handling of mercury in the blood, kidneys, and liver were evaluated and compared in rats 5 min, 1 h, and 24 h after the intravenous administration of either a 0.25 mumol/kg dose of inorganic mercury or a 0.25 mumol/kg dose of inorganic mercury plus a 0.5 mumol/kg dose of glutathione (GSH) to determine the possible role of extracellular GSH and complexes of GSH and inorganic mercury in the renal uptake and transport of inorganic mercury. Significantly more of the injected dose of inorganic mercury was present in the blood of the rats injected with inorganic mercury alone than in the blood of the rats injected simultaneously with both inorganic mercury and GSH at all times evaluated after injection. Of the mercury remaining in the blood, however, significantly more mercury was in plasma fraction of blood in the rats injected with both inorganic mercury and GSH than in the plasma fraction of blood in the rats injected with inorganic mercury alone. The blood and plasma findings indicate that much of the mercury injected with GSH was in some complex that allowed the mercury to be cleared from the blood more readily and prevented the mercury from entering readily into red blood cells. The renal concentration of mercury was significantly greater in the rats injected with both inorganic mercury and GSH than in the rats injected with inorganic mercury alone at 5 min and 1 h, but not 24 h, after injection. This increased renal accumulation of mercury during the initial hours after injection was due mainly to enhanced uptake and/or retention of mercury in the renal cortex. Urinary excretion of mercury, over 24 h, was also slightly, but significantly, greater in the rats injected with both inorganic mercury and GSH simultaneously. These data indicate that coadministration of a nontoxic dose of inorganic mercury with a twofold higher amount (in moles) of GSH increases significantly the clearance of mercury from the blood and increases the renal cortical accumulation of inorganic mercury during the initial 1 h after injection. Moreover, the data in this study are consistent with the hypothesis that extracellular GSH is an important ligand to which mercuric ions bind, and that complexes of inorganic mercury and GSH in the blood and/or ultrafiltrate probably play a role in the renal uptake of some of the mercury in blood after exposure to mercuric compounds.
在给大鼠静脉注射0.25 μmol/kg剂量的无机汞或0.25 μmol/kg剂量的无机汞加0.5 μmol/kg剂量的谷胱甘肽（GSH）后5分钟、1小时和24小时，对大鼠血液、肾脏和肝脏中汞的蓄积和处理情况进行了评估和比较，以确定细胞外GSH以及GSH与无机汞的复合物在无机汞的肾脏摄取和转运中的可能作用。在注射后评估的所有时间点，单独注射无机汞的大鼠血液中无机汞的注射剂量明显高于同时注射无机汞和GSH的大鼠血液中的含量。然而，在残留于血液中的汞中，同时注射无机汞和GSH的大鼠血液血浆部分中的汞含量明显高于单独注射无机汞的大鼠血液血浆部分中的汞含量。血液和血浆的研究结果表明，与GSH一起注射的大部分汞处于某种复合物中，这种复合物使汞更容易从血液中清除，并防止汞轻易进入红细胞。注射后5分钟和1小时，同时注射无机汞和GSH的大鼠肾脏中的汞浓度明显高于单独注射无机汞的大鼠，但在注射后24小时并非如此。注射后最初几小时肾脏中汞蓄积的增加主要是由于肾脏皮质对汞的摄取和/或保留增强。在24小时内，同时注射无机汞和GSH的大鼠的汞尿排泄量也略有但显著增加。这些数据表明，将无毒剂量的无机汞与两倍摩尔量的GSH共同给药可显著增加汞从血液中的清除率，并在注射后最初1小时内增加无机汞在肾脏皮质的蓄积。此外，本研究中的数据与以下假设一致：细胞外GSH是汞离子结合的重要配体，血液和/或超滤液中无机汞与GSH的复合物可能在接触汞化合物后血液中部分汞的肾脏摄取中起作用。
