Chronic toxicity of AsIII in mammals: The role of (GS)2AsSe-
Chronic toxicity of AsIII in mammals: The role of (GS)2AsSe-
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DOI：
10.1016/j.biochi.2009.06.004
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发表时间：
2009-10-01
期刊：
影响因子：
3.9
通讯作者：
Gailer, Juergen
中科院分区：
文献类型：
--
作者：
Gailer, Juergen
目前，数百万人主要通过摄入饮用水和食物接触到多种对环境具有持久性的有毒金属和类金属化合物。尽管生物监测研究揭示了几种有毒金属存在于普通人群的血液中，但对确定的血液浓度与其健康相关性的解释仍然是一个活跃的研究领域。为此，更好地了解哺乳动物血流中单个金属和类金属化合物的生物无机化学可以极大地促进对现有生物监测数据的解释。亚砷酸盐就是一个很好的例子，因为目前有1亿人通过饮用水接触到不安全水平的无机砷。因此，阐明毒性的潜在生物分子机制(S)至关重要，可能涉及亚砷酸盐和亚硒酸盐之间的拮抗毒性作用，这与70年前在哺乳动物中发现的作用类似。在简要综述了旨在从分子水平上了解这种微量元素拮抗作用的动物研究之后，介绍了硒-双(S-谷胱甘肽)砷离子(GS)(2)Asse-的体内形成和胆汁排泄，作为可能的生物分子基础。支持(GS)(2)Asse-在亚砷酸盐的慢性毒性和致癌性中的关键参与的论点被提出。这种毒理相关的代谢物在哺乳动物血液中的体内形成(由红细胞介导)表明，血流中发生的生物无机化学相关机制的阐明是更好地理解许多人类疾病的病因学的一种有前途的研究策略，其中一些疾病可能最终是由低水平暴露于某些无机污染物引起的。(C)2009年爱思唯尔·马森公司。版权所有。
Millions of people are currently exposed to a multitude of environmentally persistent toxic metals and metalloid compounds mainly through the ingestion of drinking water and food. Despite the fact that biomonitoring studies have revealed several toxic metals to be present in the bloodstream of the general population, the interpretation of the established blood concentrations with regard to their health relevance continues to be an active research area. To this end, a better understanding of the bioinorganic chemistry of individual metals and metalloid compounds in the mammalian bloodstream could greatly advance the interpretation of the available biomonitoring data. Arsenite represents a case in point, since >100 million people are currently exposed to unsafe levels of inorganic arsenic via drinking water. The elucidation of the underlying biomolecular mechanism(s) of toxicity is therefore of the utmost importance and could involve the antagonistic toxic effect between arsenite and selenite, which was discovered in mammals similar to 70 years ago. After a concise overview of animal studies that aimed to understand this trace element antagonism at the molecular level, the in vivo formation and biliary excretion of the seleno-bis(S-glutathionyl) arsinium ion, (GS)(2)AsSe-, is introduced as a likely biomolecular basis. Arguments in favor of a critical involvement of (GS)(2)AsSe- in the chronic toxicity and carcinogenicity of arsenite are presented. The in vivo formation of this toxicologically relevant metabolite in the mammalian bloodstream (mediated by erythrocytes) indicates that the elucidation of bioinorganic chemistry-related mechanisms that take place in the bloodstream represents a promising research strategy to better understand the etiology of numerous human diseases some of which may be ultimately caused by the low level exposure to certain inorganic pollutants. (C) 2009 Elsevier Masson SAS. All rights reserved.