The Role of Chelation in the Treatment of Arsenic and Mercury Poisoning

Abstract

Chelation for heavy metal intoxication began more than 70 years ago with the development of British anti-lewisite (BAL; dimercaprol) in wartime Britain as a potential antidote the arsenical warfare agent lewisite (dichloro[2-chlorovinyl]arsine). DMPS (unithiol) and DMSA (succimer), dithiol water-soluble analogs of BAL, were developed in the Soviet Union and China in the late 1950s. These three agents have remained the mainstay of chelation treatment of arsenic and mercury intoxication for more than half a century. Animal experiments and in some instances human data indicate that the dithiol chelators enhance arsenic and mercury excretion. Controlled animal experiments support a therapeutic role for these chelators in the prompt treatment of acute poisoning by arsenic and inorganic mercury salts. Treatment should be initiated as rapidly as possible (within minutes to a few hours), as efficacy declines or disappears as the time interval between metal exposure and onset of chelation increases. DMPS and DMSA, which have a higher therapeutic index than BAL and do not redistribute arsenic or mercury to the brain, offer advantages in clinical practice. Although chelation following chronic exposure to inorganic arsenic and inorganic mercury may accelerate metal excretion and diminish metal burden in some organs, potential therapeutic efficacy in terms of decreased morbidity and mortality is largely unestablished in cases of chronic metal intoxication.

Inhalational mercury toxicity from artisanal gold extraction reported to the Oregon poison center, 2002–2015

“…[10] Given the multitude of chelation options, and the discrepancy that exists among animal and human study results, standardized recommendations are lacking. In addition, real-world limitations of chelator availability, as demonstrated in this case, may translate to variable adherence to chelation regimens among treating providers.…”

A case of secondary diabetes mellitus associated with chronic arsenic toxicity

“…[29,[31][32][33] Moreover, there is a concern that BAL administration results in redistribution of arsenic into the brain and testes, as demonstrated in animal models. [34][35][36] DMSA was developed as a more hydrophilic analog of BAL, and therefore is associated with fewer adverse reactions. [37] In animal models, DMSA was associated with improved survival and similar arsenic elimination rates as compared to BAL.…”

Medical Countermeasures—Chelation Therapy

“…However, in the case of arsenic poisoning, chelation following chronic exposure has been shown to increase excretion but in terms of potential clinical efficacy (decreased mortality and morbidity) this is still debatable. However, in vivo studies have shown that immediate treatment with BAL, DMPS, and DMSA can avert the adverse effects of inorganic arsenic [33].…”