Amelioration of acute mercury toxicity by a novel, non-toxic lipid soluble chelator N,N %26apos; bis-(2-mercaptoethyl)isophthalamide: effect on animal survival, health, mercury excretion, and organ accumulation

作者：Clarke David; Buchanan Roger; Gupta Niladri; Haley Boyd^*

来源：Toxicological and Environmental Chemistry, 2012, 94(3): 616-640.

DOI：10.1080/02772248.2012.657199

• chelation
• mercury toxicity
• NBMI
• metal excretion
• oxidative stress
• antioxidant

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 Hg2+ 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%26apos;-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.

• 出版日期2012