THE METABOLIC REDUCTION AND NEPHROTOXIC ACTION OF TETRATHIONATE IN RELATION TO A POSSIBLE INTERACTION WITH SULFHYDRYL COMPOUNDS
THE METABOLIC REDUCTION AND NEPHROTOXIC ACTION OF TETRATHIONATE IN RELATION TO A POSSIBLE INTERACTION WITH SULFHYDRYL COMPOUNDS
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DOI：
10.1152/ajplegacy.1946.147.1.115
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发表时间：
1946-01-01
影响因子：
--
通讯作者：
STJOHN, E
中科院分区：
文献类型：
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作者：
GILMAN, A;PHILIPS, FS;STJOHN, E
在兔子和狗体内，连四硫酸盐迅速还原为硫代硫酸盐。巧合的是，观察到严重的肾毒性作用，以致于麻醉的、插入导管的狗在 30-60 分钟内完全无尿。在injn之后。中等剂量。病理检查发现近曲小管细胞出现离散性病变，30分钟内已进展至核变性阶段。可以在体外用 2,3-二巯基丙醇、1-硫代山梨醇、半胱氨酸和谷胱甘肽还原连四硫酸盐，并以化学计量形成相应的二硫化物。从预防性给药的事实可以明显看出，硫醇在体内可以与连四硫酸盐发生反应。 1-硫代山梨醇或半胱氨酸可防止连四硫酸盐的肾毒性作用。有证据表明连四硫酸盐的分布和还原位点是细胞外的。提出了两种替代理论：1，连四硫酸盐选择性地渗透近端肾小管的细胞，对依赖于[长划线]SH 的催化系统发挥直接毒性作用，或 2，通过去除可扩散的[长划线]SH 化合物选择性地损伤近端肾小管的细胞。
In the rabbit and the dog, tetrathionate is rapidly reduced to thiosulfate. Coincidently there is observed a nephrotoxic action of such severity that in anesthetized, catheterized dogs complete anuria results within 30-60 mins. after the injn. of moderate doses. Pathological examination reveals a discrete lesion of the cells of the proximal tubule which has advanced to the stage of nuclear degeneration within 30 min. It is possible to reduce tetrathionate in vitro with 2,3-dimercaptopropanol, 1-thiosorbitol, cysteine, and glutathione with the stoichiometric formation of the corresponding disulfides. That thiols can react with tetrathionate in vivo is evident from the fact that the prophylactic admn. of 1-thiosorbitol or cysteine protects against the nephrotoxic action of tetrathionate. Evidence is presented that the distribution and site of reduction of tetrathionate are extracellular. Two alternative theories are presented that 1, tetrathionate selectively permeates the cells of the proximal tubule to exert a direct toxic action on catalytic systems dependent on the presence of [long dash]SH, or 2, the cells of the proximal tubules are selectively damaged by the removal of diffusible [long dash]SH compounds.