ARSINE METABOLISM AND MECHANISM OF TOXICITY

砷化氢是一种重要的有毒物质，但研究较少 尽管其在半导体工业中广泛使用。 此外 在工业上，当酸或碱收缩时， 无机砷和元素金属，如铝、锡、锌， 他人 因此，我们预测它可以在环境中形成， 危险废物倾倒场等场所。 砷化氢的主要毒性途径是大量溶血。 胂 暴露是一个严重的问题，因为没有治疗， 完全血液交换。 因此，一场大规模的事故将耗尽 即使是最大的血库的血液储备。 令人惊讶的是，砷化氢没有得到更多的关注， 它被广泛使用，并且在接触后没有良好的治疗方法。 该提案将研究砷化氢溶血的机制， 描述胂分子中发生的变化， 最终设计出有效的治疗方法 主要假设 砷化氢首先与血红蛋白结合， 氧化的胂产物和活性氧物质。 活性氧 然后与细胞成分发生反应， 以类似于其他溶血剂的方式溶血。 第二 假设也被认为是血红蛋白反应在一个类似的 以P-450的方式，形成反应性胂代谢物，然后 会攻击重要的细胞成分 这里提出的研究联合收割机结合了一种使用核的化学方法， 磁共振和电子自旋共振光谱， 用生物学研究表征砷化氢-血红蛋白相互作用 其表征了红细胞上的氧化应激。 其他 目的包括对形成的砷化氢物种进行表征， 检查氧饱和度对溶血的作用。 我们 目的是利用这些结果来设计一种合理的治疗方法， 砷中毒

Arsine is an important toxicant which has received little study despite its extensive use in the semiconductor industry. In addition to its industrial use, it can be formed when acid or base contracts inorganic arsenic and elemental metals like aluminum, tin, zinc and others. Thus, we predict that it can be formed in the environment in such places as hazardous waste dumpsites. The major route of toxicity for arsine is massive hemolysis. Arsine exposure ia a serious problem because there is no treatment except total blood exchange. Thus, a large scale accident would deplete the blood reserves of even the largest of blood banks. It is surprising that arsine has not received more attention because it is in widespread use and there is no good treatment after exposure. This proposal will study the mechanism of arsine-based hemolysis and characterize the changes which occur in the arsine molecule as a means to eventually design an effective treatment. The primary hypothesis is that arsine binds hemoglobin as first step and then reacts to form an oxidized arsine product and active oxygen species. Active oxygen species then go on to react with cellular components to cause hemolysis in a manner similar to other hemolytic agents. A second hypothesis is also considered in which hemoglobin reacts in a similar manner to P-450 and forms a reactive arsine metabolite which then could attack important cellular constituents. The studies proposed here combine a chemical approach using nuclear magnetic resonance and electron spin resonance spectroscopy to characterize the arsine-hemoglobin interaction with biological studies which characterize the oxidant stress on the red blood cell. Other aims include the characterization of the arsine species formed and an examination of the role of oxygen saturation on hemolysis. Our objective is to use these results to design a rational treatment for arsine toxicity.