Antidotal efficacy of newly synthesized dimercaptosuccinic acid (DMSA) monoesters in experimental arsenic poisoning in mice

Fundam Appl Toxicol. 1995 Jul;26(2):239-45. doi: 10.1006/faat.1995.1094.

Abstract

The efficacy of four newly synthesized monoesters of meso-2,3-dimercaptosuccinic acid (DMSA), mono-i-amyl- (Mi-ADMS), mono-n-amyl- (Mn-ADMS), mono-i-butyl- (Mi-BDMS), and mono-n-butyl-meso-2,3-dimercaptosuccinate (Mn-BDMS) in increasing survival and arsenic elimination in experimental arsenic poisoning was investigated. Male mice (strain NMRI) received arsenite sc (survival study: 130 mumol/kg, 7 mice/group; elimination study: 85 mumol/kg (LD5) together with a tracer dose of 73As(III), 6 mice/group). After 30 min mice were treated with 0.7 mmol/kg of DMSA or a monoester ip or via gastric tube (ig). Control animals received saline ip. In the survival study mice were observed for 30 days. In the elimination study, the 73-arsenic content of several organs (blood, liver, heart, lung, kidneys, spleen, testes, brain, small intestine, large intestine, muscle, and skin) was measured 0.5, 2, 4, 6, and 8 hr after the arsenic injection using a gamma counter. Survival increased correspondingly well with the increase of arsenic elimination. DMSA, Mi-ADMS, Mn-ADMS, Mi-BDMS, and Mn-BDMS markedly decreased arsenic content in most organs as soon as 1.5 hr after treatment. Only in small and large intestine were higher arsenic amounts found, indicating a shift in arsenic elimination from the renal to the fecal route, and thereby suggesting a protective effect for the kidneys. Given ip, the monoesters turned out to be similarly as effective as the parent drug DMSA. Following ig treatment, the DMSA monoesters Mi-ADMS and Mn-ADMS seemed to be superior to DMSA with regard to survival.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Animals
  • Antidotes / chemistry
  • Antidotes / pharmacology*
  • Arsenic Poisoning*
  • Arsenic Trioxide
  • Arsenicals / antagonists & inhibitors*
  • Brain / drug effects
  • Esters / pharmacology
  • Intestine, Large / drug effects
  • Intestine, Small / drug effects
  • Kidney / drug effects
  • Male
  • Mice
  • Mice, Inbred Strains
  • Oxides / antagonists & inhibitors*
  • Oxides / toxicity*
  • Succimer / chemical synthesis
  • Succimer / chemistry
  • Succimer / toxicity*

Substances

  • Antidotes
  • Arsenicals
  • Esters
  • Oxides
  • Succimer
  • Arsenic Trioxide