Sequence of toxic events in arsine-induced hemolysis in vitro: implications for the mechanism of toxicity in human erythrocytes.
Sequence of toxic events in arsine-induced hemolysis in vitro: implications for the mechanism of toxicity in human erythrocytes.
复制标题
体外砷化氢诱导溶血的毒性事件序列：对人红细胞毒性机制的影响。
DOI：
10.1006/faat.1997.2339
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Carter,DE
中科院分区：
文献类型：
--
作者：
Winski,SL;Barber,DS;Rael,LT;Carter,DE
砷氢化物（AsH 3）是砷的最急性毒性形式，在暴露后引起快速和严重的溶血。作用机制尚不清楚，在受控系统中很少有详细的毒性研究。为了检测砷化氢溶血并了解各种毒性反应的重要性，将人红细胞与砷化氢体外孵育，并确定毒性标志物随时间的变化。最早的损伤指标是钠和钾水平的变化。在与ImM砷化氢孵育5分钟内，细胞失去体积控制，表现为钾的渗漏、钠的内流和血细胞比容的增加。然而，砷化氢并没有显著改变ATP水平，也没有抑制ATP酶。这些变化之后，膜超微结构（光镜和电镜检查）的深刻干扰。到10分钟时，形成了大量受损细胞，并且它们的数量随时间增加。这些事件之前溶血，这是不显着的，直到30分钟。有人提出，砷化氢与血红蛋白相互作用，形成有毒的血红蛋白氧化产物，这也被调查作为一个潜在的原因溶血。基本上与砷化氢接触，高铁血红蛋白形成，但只有达到2-3%的总细胞血红蛋白，并保持不变，长达90分钟。没有证据表明，进一步的氧化产物（氯化血红素和海因茨机构）在这个系统中形成。基于这些观察结果，溶血似乎依赖于血红蛋白氧化以外的机制引起的膜破坏。
Arsine, the hydride of arsenic (AsH3), is the most acutely toxic form of arsenic, causing rapid and severe hemolysis upon exposure. The mechanism of action is not known, and there are few detailed investigations of the toxicity in a controlled system. To examine arsine hemolysis and understand the importance of various toxic responses, human erythrocytes were incubated with arsinein vitro, and markers of toxicity were determined as a function of time. The earliest indicators of damage were changes in sodium and potassium levels. Within 5 min incubation with 1 mM arsine, the cells lost volume control, manifested by leakage of potassium, influx of sodium, and increases in hematocrit. Arsine did not, however, significantly alter ATP levels nor inhibit ATPases. These changes were followed by profound disturbances in membrane ultrastructure (examined by light and electron microscopy). By 10 min, significant numbers of damaged cells formed, and their numbers increased over time. These events preceded hemolysis, which was not significant until 30 min. It has been proposed that arsine interacts with hemoglobin to form toxic hemoglobin oxidation products, and this was also investigated as a potential cause of hemolysis. Essentially on contact with arsine, methemoglobin was formed but only reached 2–3% of the total cellular hemoglobin and remained unchanged for up to 90 min. There was no evidence that further oxidation products (hemin and Heinz bodies) were formed in this system. Based on these observations, hemolysis appears to be dependent on membrane disruption by a mechanism other than hemoglobin oxidation.