David Clarke, Roger Buchanan, Niladri Gupta, Boyd Haley
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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.
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.
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.