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Journal Article

Dimercaptosuccinic Acid (DMSA), A Non-Toxic, Water-Soluble Treatment For Heavy Metal Toxicity

01 Jun 1998-Alternative medicine review : a journal of clinical therapeutic (Altern Med Rev)-Vol. 3, Iss: 3, pp 199-207
TL;DR: DMSA is a sulfhydryl-containing, water-soluble, non-toxic, orally-administered metal chelator which has been in use as an antidote to heavy metal toxicity since the 1950s and is established as the premier metal chelation compound, based on oral dosing, urinary excretion, and its safety characteristics compared to other chelating substances.
Abstract: Heavy metals are, unfortunately, present in the air, water, and food supply. Cases of severe acute lead, mercury, arsenic, and cadmium poisoning are rare; however, when they do occur an effective, non-toxic treatment is essential. In addition, chronic, low-level exposure to lead in the soil and in residues of lead-based paint; to mercury in the atmosphere, in dental amalgams and in seafood; and to cadmium and arsenic in the environment and in cigarette smoke is much more common than acute exposure. Meso-2,3-dimercaptosuccinic acid (DMSA) is a sulfhydryl-containing, water-soluble, non-toxic, orally-administered metal chelator which has been in use as an antidote to heavy metal toxicity since the 1950s. More recent clinical use and research substantiates this compound’s efficacy and safety, and establishes it as the premier metal chelation compound, based on oral dosing, urinary excretion, and its safety characteristics compared to other chelating substances. (Altern Med Rev 1998;3(3):199-207)

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Citations
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Journal ArticleDOI
TL;DR: This review provides an update of the existing chelating agents and the various strategies available for the treatment of heavy metals and metalloid intoxications.
Abstract: Chelation therapy is the preferred medical treatment for reducing the toxic effects of metals. Chelating agents are capable of binding to toxic metal ions to form complex structures which are easily excreted from the body removing them from intracellular or extracellular spaces. 2,3-Dimercaprol has long been the mainstay of chelation therapy for lead or arsenic poisoning, however its serious side effects have led researchers to develop less toxic analogues. Hydrophilic chelators like meso-2,3-dimercaptosuccinic acid effectively promote renal metal excretion, but their ability to access intracellular metals is weak. Newer strategies to address these drawbacks like combination therapy (use of structurally different chelating agents) or co-administration of antioxidants have been reported recently. In this review we provide an update of the existing chelating agents and the various strategies available for the treatment of heavy metals and metalloid intoxications.

765 citations


Cites background from "Dimercaptosuccinic Acid (DMSA), A N..."

  • ...The drug is 95 % plasma protein bound, most likely by virtue of binding on one of its sulfhydryl groups to a cysteine residue on albumin, leaving the other –SH available to chelate metals [39]....

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01 Apr 2011-BMJ

729 citations

Journal ArticleDOI
TL;DR: Superparamagnetic iron oxide (Fe3O4) nanoparticles with a surface functionalization of dimercaptosuccinic acid (DMSA) are an effective sorbent material for toxic soft metals such as Hg, Ag, Pb, Cd, and Tl, which effectively bind to the DMSA ligands and for As, which binds to the iron oxide lattices.
Abstract: We have shown that superparamagnetic iron oxide (Fe3O4) nanoparticles with a surface functionalization of dimercaptosuccinic acid (DMSA) are an effective sorbent material for toxic soft metals such as Hg, Ag, Pb, Cd, and Tl, which effectively bind to the DMSA ligands and for As, which binds to the iron oxide lattices. The nanoparticles are highly dispersible and stable in solutions, have a large surface area (114 m2/g), and have a high functional group content (1.8 mmol thiols/g). They are attracted to a magnetic field and can be separated from solution within a minute with a 1.2 T magnet. The chemical affinity, capacity, kinetics, and stability of the magnetic nanoparticles were compared to those of conventional resin based sorbents (GT-73), activated carbon, and nanoporous silica (SAMMS) of similar surface chemistries in river water, groundwater, seawater, and human blood and plasma. DMSA-Fe3O4 had a capacity of 227 mg of Hg/g, a 30-fold larger value than GT-73. The nanoparticles removed 99 wt % of 1 mg...

634 citations

Journal ArticleDOI
TL;DR: Considerable attention was given in this review to pediatric methylmercury exposure and neurodevelopment because it is the most thoroughly investigated Hg species.

477 citations


Cites background from "Dimercaptosuccinic Acid (DMSA), A N..."

  • ...They found highly elevated pretreatment Hg levels in urine, which they reduced therapeutically with a succimer (DMSA) treatment regimen (Forman et al., 2000; Miller, 1998)....

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Journal Article
TL;DR: Basic research pertaining to the transport of toxic metals into the brain is summarized, and a case is made for the use of hydrolyzed whey protein to support metal detoxification and neurological function.
Abstract: Chronic, low level exposure to toxic metals is an increasing global problem. The symptoms associated with the slow accumulation of toxic metals are multiple and rather nondescript, and overt expression of toxic effects may not appear until later in life. The sulfhydryl-reactive metals (mercury, cadmium, lead, arsenic) are particularly insidious and can affect a vast array of biochemical and nutritional processes. The primary mechanisms by which the sulfhydryl-reactive metals elicit their toxic effects are summarized. The pro-oxidative effects of the metals are compounded by the fact that the metals also inhibit antioxidative enzymes and deplete intracellular glutathione. The metals also have the potential to disrupt the metabolism and biological activities of many proteins due to their high affinity for free sulfhydryl groups. Cysteine has a pivotal role in inducible, endogenous detoxication mechanisms in the body, and metal exposure taxes cysteine status. The protective effects of glutathione and the metallothioneins are discussed in detail. Basic research pertaining to the transport of toxic metals into the brain is summarized, and a case is made for the use of hydrolyzed whey protein to support metal detoxification and neurological function. Metal exposure also affects essential element status, which can further decrease antioxidation and detoxification processes. Early detection and treatment of metal burden is important for successful detoxification, and optimization of nutritional status is paramount to the prevention and treatment of metal toxicity.

287 citations

References
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Journal ArticleDOI
TL;DR: The results show that hydrophilic DMPS and DMSA may fail to rapidly and completely remove arsenic that has escaped from the extracellular space across tight epithelial barriers, but owing to their low toxicity, which allows larger doses to be applied, and the potential modification of their pharmacokinetics by means of inert oral anion-exchange resins,DMPS andDMSA may advantageously replace BAL when ever intervention time is not critical.
Abstract: 1 Dimercaprol (BAL), 2,3-dimercaptopropanesulpho nate sodium (DMPS) and meso-2,3-dimercaptosucci nic acid (DMSA) are effective arsenic antidotes, but the question which one is preferable for optimal therapy of arsenic poisoning is still open to discussion. Major drawbacks of BAL include (a) its low therapeutic index, (b) its tendency to redistribute arsenic to brain and testes, for example, (c) the need for (painful) intramuscular injection and (d) its unpleasant odour.2 The newer antidotes DMPS and DMSA feature low toxicity and high therapeutic index. They can be given orally or intravenously due to their high water solubility. While these advantages make it likely that DMPS and DMSA will replace BAL for the treatment of chronic arsenic poisoning, acute intoxication - espe cially with lipophilic organoarsenicals - may pose a problem for the hydrophilic antidotes, because their ionic nature can adversely affect intracellular avail ability.3 This article focuses on aspects dealing with the power of BAL, DM...

66 citations


"Dimercaptosuccinic Acid (DMSA), A N..." refers background or methods in this paper

  • ...DMSA has also been used effectively in arsenic and cadmium poisoning.(2,3,52)...

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  • ...DMSA’s water solubility and oral dosing create a distinct advantage over BAL, which has a small therapeutic index and must be administered in an oil solution via painful, deep intramuscular injection.(2) DMSA, on the other hand, has a large therapeutic window and is the least toxic of the dithiol compounds....

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Journal ArticleDOI
TL;DR: Since the toxicity of dimercaptosuccinate seems to be almost as low as that of D-penicillamine this dithiol may provide a potentially useful agent in clinical poisoning due to methyl mercury.
Abstract: Treatment with 2,3-dimercaptosuccinic acid was more effective than N-acetyl-DL-penicillamine and monomercaptosuccinic acid in mobilizing mercury from mice after the injection of methyl mercuric chloride. Dimercaptosuccinic acid treatment started 4 days after the mercury injection and given for 8 days at a dose of 1 mmol SH/kg per day removed more than 2/3 of the mercury in the brain, while acetylpenicillamine and mercaptosuccinate correspondingly removed less than 1/2 of the brain deposits. Neither treatment with 2,3-dimercaptopropano-1-sulphonate nor with a new thiolated resin, mercaptostarch, mobilized significant amounts of mercury from the brain. Since the toxicity of dimercaptosuccinate seems to be almost as low as that of D-penicillamine this dithiol may provide a potentially useful agent in clinical poisoning due to methyl mercury.

66 citations

Journal ArticleDOI
TL;DR: The data suggest that after a few days of cessation of occupational exposure to mercury vapour the HgU before and after administration of DMSA mainly reflects the amount of mercury stored in the kidney, which represents a mercury pool with a slow turnover.
Abstract: The spontaneous and chelator mediated excretion of mercury in urine was investigated in male subjects occupationally exposed to mercury vapour (alkaline battery and chloralkali plants) who did not exhibit any sign of kidney damage. The time course of the spontaneous elimination of mercury in urine was examined in seven workers (age 22-40) who had been removed from exposure to mercury vapour (average duration of exposure 4.4 years) because their urinary mercury concentrations repeatedly exceeded 100 micrograms/g creatinine. The post exposure observation period started 10 to 29 days after the date of removal and lasted about 300 days (slow HgU elimination phase). For each worker, the kinetics of the spontaneous HgU decline followed a first order process; the biological half life ranged from 69 to 109 days (mean 90 days). The increased urinary excretion of mercury after a single oral administration of 2 g meso-2,3-dimercaptosuccinic acid (DMSA) was investigated in 16 control workers (group A; age 23 to 49), in 11 workers removed from exposure for at least two years (group B; age 27 to 41), and in 16 workers currently exposed to mercury vapour (group C; age 21 to 58). In group C, the DMSA experiment was repeated twice (three weeks before and three weeks after a holiday) after measures had been taken to reduce the mercury emission. The urinary mercury excretion was significantly higher during the 24 hours after DMSA administration in all groups compared with that in the 24 hours before. The bulk (50-70%) of the DMSA stimulated mercury excretion appeared within the first eight hours. In each group, the amount of mercury (microgram Hg/24h) excreted after DMSA was significantly correlated with that before administration of DMSA. The groups whose exposure had ceased, however, exhibited much higher correlation for coefficients (r=0.97 for group B and 0.86 for group C after three weeks of holiday) than those currently exposed to mercury vapour (r-0.66 for group C before and 9.58 after reduction of exposure). The data suggest that after a few days of cessation of occupational exposure to mercury vapour the HgU before and after administration of DMSA mainly reflects the amount of mercury stored in the kidney, which represents a mercury pool with a slow turnover.

65 citations

Journal ArticleDOI
TL;DR: According to the conclusions of independent evaluations from different state health agencies, the release of mercury from dental amalgam does not present any non-acceptable risk to the general population.
Abstract: This paper summarizes some recent reports on mercury release from amalgam fillings and resulting concentrations in biological fluids, development of antibiotic resistance, and kidney function. In a series of studies of subjects with amalgam fillings, mercury (Hg) levels were followed in saliva, feces, blood, plasma, and urine before and until 60 d after removal of all of the fillings. The Hg concentrations in saliva remained elevated for at least 1 wk, suggesting that dissolved Hg vapor is not the major source of mercury in mixed saliva. An absorption phase of Hg was seen in plasma during 24 h after amalgam removal. After 60 d the plasma Hg concentration was reduced to 40%, of the baseline level. The decrease per amalgam surface was 0.11 nmol/l (range 0.02 0.40). The Hg level in feces increased two orders of magnitude two days after amalgam removal. At day 60, the median Hg concentration was still slightly higher than the median value of the amalgam free control group. The resistance patterns of the oral and intestinal microflora in these subjects were also studied. In the intestinal microflora, the relative amount of intestinal microorganisms resistant to 50 microM HgCl2 peaked 7 d after removal of the amalgam fillings, with a median value per sample of 6.1%, compared to 1.3% in samples collected prior to the Hg exposure. However, no statistical differences in the resistance pattern of the oral microflora were detected between the control and the experimental groups. A number of sensitive kidney function parameters were measured 1 wk before and 1, 2, and 60 d after amalgam removal. No effects on the various kidney parameters studied were recorded. According to the conclusions of independent evaluations from different state health agencies, the release of mercury from dental amalgam does not present any non-acceptable risk to the general population.

64 citations

Journal ArticleDOI
TL;DR: The formation of these water soluble DMSA-cysteine mixed disulfides indicate a thiol-disulfide interchange between DMSA and L-cystine and should encourage the evaluation of DMSA in the treatment of cystinuria.

59 citations