Effect of dithiothreitol on mercuric chloride- and uranyl nitrate-induced acute renal failure in the rat.
Effect of dithiothreitol on mercuric chloride- and uranyl nitrate-induced acute renal failure in the rat.
复制标题
二硫苏糖醇对氯化汞和硝酸铀酰诱导的大鼠急性肾衰竭的影响。
DOI：
10.1038/ki.1977.88
复制
发表时间：
1977
影响因子：
19.6
通讯作者：
W. Flamenbaum
中科院分区：
文献类型：
--
作者：
J. Kleinman;J. S. McNeil;J. Schwartz;R. Hamburger;W. Flamenbaum
本研究旨在探讨巯基还原剂和重金属螯合剂二硫苏糖醇（DDT）对重金属诱导的大鼠急性肾功能衰竭过程的影响。代谢笼中的大鼠组接受硝酸铀酰（UN）单独，UN + DTT，氯化汞（HgCl 2）单独，和HgCl 2 + DTT。在研究的48小时内，单独注射UN产生氮质血症、肌酐清除率降低和钠排泄分数升高。在注射UN后30 min给予DTT时，未观察到UN对肾功能的这些影响。HgCl 2诱导的急性肾功能衰竭获得了定性相似的结果。各组大鼠在UN + DTT、单独HgCl 2或HgCl 2 + DTT后6小时处死，并进行血浆肾素活性（PRA）和浅表及深部肾小球体（JGA）的肾素活性测定。PRA和JGA肾素增加，在动物接受UN或氯化汞单独，但不是在大鼠接受DTT和UN或氯化汞。还研究了DTT对~（203）Hg分布的影响。DTT治疗并没有改变肾脏积累的203汞，这表明，这种代理不通过限制肾脏暴露于重金属。因此，DTT改善了重金属诱导的ARF的过程，并且这种效果与预防重金属诱导的钠排泄和肾素-血管紧张素系统活性的改变有关。
The current study was undertaken to examine the effects of dithiothreitol (DDT), a sulfhydryl-reducing agent and heavy metal chelator, on the course of heavy metal-induced acute renal failure in the rat. Groups of rats in metabolic cages received uranyl nitrate (UN) alone, UN plus DTT, mercuric chloride (HgCl2) alone, and HgCl2 plus DTT. UN injected alone produced azotemia, decreased creatinine clearance, and rising fractional sodium excretion over the 48 hr of study. These effects of UN on renal function were not observed when DTT was administered 30 min after UN injection. Qualitatively similar results were obtained with HgCl2-induced acute renal failure. Groups of rats were killed at 6 hr after UN plus DTT, HgCl2 alone, or HgCl2 plus DTT; and determinations of plasma renin activity (PRA) and renin activities of the superficial and deep juxtaglomerular apparatus (JGA) were performed. PRA's and JGA renins were increased in animals receiving either UN or HgCl2 alone, but not in the rats receiving both DTT and UN or HgCl2. The effect of DTT on distribution of 203Hg was also examined. Treatment with DTT did not alter the renal accumulation of 203Hg, suggesting that this agent does not act by limiting renal exposure to the heavy metals. Thus, DTT ameliorates the course of heavy metal-induced ARF, and this effect is associated with prevention of heavy metal-induced alterations in sodium excretion and renin-angiotensin system activity.