Amelioration of Acute Mercury Toxicity by a Novel, Non-Toxic Lipid Soluble Chelator N,N'bis-(2-mercaptoethyl)isophthalamide: Effect on Animal Survival, Health, Mercury Excretion and Organ Accumulation.

IF 1.1 4区 环境科学与生态学 Q4 ENVIRONMENTAL SCIENCES
David Clarke, Roger Buchanan, Niladri Gupta, Boyd Haley
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引用次数: 0

Abstract

The toxic effects of mercury are known to be complex with specific enzyme inhibitions and subsequent oxidative stress adding to the damaging effects. There are likely other factors involved, such as the development of impaired metal ion homeostasis and depletion of thiol and selenium based metabolites such as cysteine and selenium. Much of the toxicity of mercury occurs at the intracellular level via binding of Hg(2+) to thiol groups in specific proteins. Therefore, amelioration of mercury toxicity by the use of chelation would likely be enhanced by the use of a chelator that could cross the cell membrane and the blood brain barrier. It would be most favorable if this compound was of low toxicity, had appropriate pharmacokinetics, bound and rendered mercury cation non-toxic and had antioxidant properties. Herein we report on such a chelator, N,N'-bis(2-mercaptoethyl)isophthalamide (NBMI), and, using an animal model, show that it prevented the toxic effects associated with acute exposure induced by injected mercury chloride.

新型无毒脂溶性螯合剂 N,N'双-(2-巯基乙基)间苯二甲酰胺对急性汞毒性的改善:对动物生存、健康、汞排泄和器官积累的影响
众所周知,汞的毒性作用是复杂的,特定的酶抑制和随后的氧化应激会增加其破坏性影响。可能还涉及其他因素,如金属离子平衡受损、半胱氨酸和硒等以硫醇和硒为基础的代谢物耗竭。汞的毒性主要是通过 Hg(2+) 与特定蛋白质中的硫醇基结合而在细胞内产生的。因此,使用能穿过细胞膜和血脑屏障的螯合剂可能会增强螯合剂对汞毒性的改善作用。如果这种化合物毒性低、具有适当的药代动力学、能与汞阳离子结合并使其无毒,而且具有抗氧化特性,那将是最有利的。在此,我们报告了这样一种螯合剂--N,N'-双(2-巯基乙基)间苯二甲酰胺(NBMI),并利用动物模型表明,它能防止与注射氯化汞引起的急性接触相关的毒性效应。
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来源期刊
Toxicological and Environmental Chemistry
Toxicological and Environmental Chemistry ENVIRONMENTAL SCIENCES-TOXICOLOGY
CiteScore
3.50
自引率
5.60%
发文量
0
期刊介绍: The journal is interdisciplinary in outlook, and manuscripts published in it cover all relevant areas: • inorganic chemistry – trace elements in food and the environment, metal complexes and chelates; • organic chemistry – environmental fate, chemical reactions, metabolites and secondary products, synthesis of standards and labelled materials; • physical chemistry – photochemistry, radiochemistry; • environmental chemistry – sources, fate, and sinks of xenochemicals, environmental partitioning and transport, degradation and deposition; • analytical chemistry – development and optimisation of analytical methods, instrumental and methodological advances, miniaturisation and automation; • biological chemistry – pharmacology and toxicology, uptake, metabolism, disposition of xenochemicals, structure-activity relationships, modes of action, ecotoxicological testing.
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