Structural alterations in the rat kidney after acute arsine exposure.
Structural alterations in the rat kidney after acute arsine exposure.
复制标题
急性砷化氢暴露后大鼠肾脏的结构变化。
DOI：
10.1038/labinvest.3780012
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Carter,DE
中科院分区：
文献类型：
--
作者：
Ayala-Fierro,F;Baldwin,AL;Wilson,LM;Valeski,JE;Carter,DE
砷化氢（AsH 3）的毒性机制尚未完全阐明.本研究采用原代培养的大鼠肾皮质上皮细胞和原位分离的大鼠肾脏，测定了AsH 3及其溶血产物的毒性。本研究的目的是建立AsH 3暴露引起的肾功能损害模型.假设未改变的AsH 3和AsH 3产生的溶血产物可能含有亚砷酸盐（As（III））作为代谢产物，这两种物质都是肾毒性的原因。通过2，3-双[2-甲氧基-4-硝基-5-磺基苯基]-2H-四唑-5-甲酰苯胺内盐（XTT）生物还原、细胞内钾（K+）和乳酸脱氢酶（LDH）渗漏测定离体细胞的毒性。来自XTT生物还原的数据表明，大多数毒性发生在1小时，并且与砷的种类无关。在4小时，观察到的毒性取决于砷的种类，并产生的As（III）。在分离的细胞中，As（III）-掺入溶血产物产生类似的毒性，细胞内K+和LDH。AsH 3-溶血产物仅在1h时影响LDH。AsH 3对离体大鼠肾脏有很强的毒性作用。在该系统中，AsH 3暴露10分钟后，毒性作用主要表现在肾小球和管周内皮细胞。肾小管上皮细胞也出现早期毒性迹象。AsH 3-溶血产物在暴露10分钟后没有毒性。这些数据表明，早期的细胞毒性所造成的不变AsH 3的结果在肾功能障碍，产生AsH 3，后来形成的溶血产物，可能含有砷（III）。这些结果对了解AsH 3中毒后的肾毒性作用有重要意义.
The mechanism of arsine (AsH 3) toxicity is not completely understood. In this investigation, the toxicity of AsH 3 and AsH 3-produced hemolytic products was determined in primary culture of renal cortical epithelial cells and in the in situ isolated rat kidney. The objective of this study was to model kidney dysfunction caused by AsH 3 exposure. The hypothesis was that unchanged AsH 3 and AsH 3-produced hemolysate that may contain arsenite (As (III)) as metabolite are both responsible for renal toxicity. Toxicity in isolated cells was determined by 2, 3-bis [2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt (XTT) bioreduction, intracellular potassium (K+), and lactate dehydrogenase (LDH) leakage. Data from XTT bioreduction showed that most toxicity occurred at 1 hour and was independent of the arsenic species. At 4 hours, the observed toxicity depended on the arsenic species and was generated by As (III). In the isolated cells, the As (III)-spiked hemolysate produced similar toxicities with regard to intracellular K+ and LDH. The AsH 3-hemolysate only affected LDH at 1 hour. Unchanged AsH 3 was very toxic to the isolated rat kidney. In this system, after 10 minutes exposure to AsH 3, the effects of toxicity were observed mainly in the glomerular and peritubular endothelial cells. Tubular epithelial cells also presented early signs of toxicity. The AsH 3-hemolysate was not toxic after a 10-minute exposure. These data suggested that early cytotoxicity caused by unchanged AsH 3 results in kidney dysfunction, produced by AsH 3, and later by the formation of a hemolysate that may contain As (III). These data may be important in understanding the renal toxic effects after AsH 3 intoxication.
影响因子：
10.5
作者：
EVANS, MJ;SCARPULLA, RC
通讯作者：
SCARPULLA, RC