The Effect of Immediate and Delayed Treatment with 2,3‐Dimercaptopropane‐l‐sulphonate on the Distribution and Toxicity of Inorganic Mercury in Mice and in Foetal and Adult Rats

Abstract

The distribution and excretion of mercury were studied in mice and rats given a single injection of HgC12 combined with chelation treatment. BAL-sulph (2,3-dimercaptopropane-l-sulphonate) given intravenously (500 pmol SH/kg) to mice 24 hrs after the mercury injection (2.0 pmol Hg/kg) reduced the kidney Hglevel significantly, while NAPA (N-acetyl-DL-penicillamine) and BAL (2,3-dimercaptopropanol) did not. Severe kidney damage with oliguria was observed in pregnant as well as in non-pregnant rats after injection of 5pmol/kg of HgCL2. The gross pathological changes could be avoided with immediate treatment with BALsulph (500pmol SH/kg), and such treatment protected against the oliguric reaction. Treatment delayed for 24 hrs reduced the renal Hg-levels significantly, but was ineffective in preventing the kidney damage. This indicates that irreversible changes might have occurred in kidneys cells at this time. TheHg-levels in the brain were either unchanged or lowered in animals given BAL-sulph treatment. BAL-sulph is supposed to act by chelation of Hg", particularly in the extracellular space. The complexes formed appears to be rapidly excreted by healthy kidneys. Mercury poisoning with severe renal damage is, however, associated with a block in urinary Hgexcretion. The poisoned animals responded on the BAL-sulph treatment with a substantial raise of faecal mercury excretion.

Effect of DMPS and DMSA on the Placental and Fetal Disposition of Methylmercury

“…Less is known about the mechanisms by which mercuric ions are removed from fetal tissues and are transported back into maternal blood. DMPS has been shown to extract mercuric ions from fetuses and placentas whose mothers were exposed to a form of inorganic mercury, i.e., mercuric chloride [22]. However, to our knowledge, there are no studies examining the effect of DMPS and DMSA on the disposition of mercuric ions in placental and fetal tissues following maternal exposure to a form of organic mercury, i.e., CH 3 Hg + .…”

“…Interestingly, administration of DMPS to pregnant mice exposed orally to CH 3 Hg + appeared to protect fetuses from the toxic effects of methylmercury [21]. Similarly, a separate study in rats suggests that DMPS is capable of extracting mercuric ions from fetal and placental tissues following maternal exposure to inorganic mercury [22]. Currently, there is no evidence indicating that either, DMPS or DMSA is capable of extracting mercuric ions from placental and fetal tissues of dams exposed to a form of organic mercury, CH 3 Hg + .…”

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

“…In a lower dose rat model examining acute nephrotoxicity of mercuric chloride (1.4 mg/kg iv), immediate treatment with DMPS (54 mg/ kg iv) averted oliguric renal failure. However, if the DMPS were administered after a delay of 24 h, the protective effect was lost (Table 3) [18]. The time dependence of efficacy was also shown in another rat model of mercuric chloride intoxication (1 mg/kg iv) [19].…”

Chelation for Heavy Metals (Arsenic, Lead, and Mercury): Protective or Perilous?

“…noted that all the animals survived when a single dose of the antidote was administered 5 min after the arsenical, as compared with no survival despite intensive repeated chelation initiated after a delay of 6 h. This finding that “chelation delayed is chelation diminished” has been demonstrated for other chelators studied in the context of acute intoxication by inorganic arsenic or mercuric salts. 7 , 8 , 9 Although chelation initiated late in the clinical course may still enhance urinary excretion of the metal, there can be no assurance that such delayed decorporation will influence the key measure of therapeutic efficacy, namely decreased morbidity and mortality.…”