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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: It is concluded that intraoral air is a reliable physiological indicator of Hg released from dental amalgam that may reflect a major source of chronic Hg exposure.
Abstract: Intra-oral air was analyzed for mercury (Hg) vapor concentration in 46 subjects, 35 of whom had dental amalgam restorations. Measurements were made with a Jerome Hg detector both before and ten min after chewing stimulation. Subjects with dental amalgams had unstimulated Hg vapor concentrations that were nine times greater than basal levels in control subjects with no amalgams. Chewing stimulation in subjects with amalgams increased their Hg concentration six-fold over unstimulated Hg levels, or a 54-fold increase over levels observed in control subjects. Concentrations of Hg measured in intra-oral air larger than those reported in expired air were attributed to the rate and direction of air passage across amalgam surfaces. There were significant correlations between Hg vapor released into intra-oral air after chewing stimulation and the numbers and types of amalgam restorations. It is concluded that intraoral air is a reliable physiological indicator of Hg released from dental amalgam that may reflect a major source of chronic Hg exposure.

169 citations

Journal ArticleDOI
TL;DR: The identification of GSH as an endogenous complexing agent in the transport of metals between tissues and body fluids now permits the design of therapeutic strategies aimed at exploiting this transport vehicle to effect the removal of metals via physiological routes of excretion.

166 citations

Journal Article
TL;DR: Tissue analyses indicated that Pb was mobilized from bone and kidney and redistributed initially to both brain and liver, and it is suggested that a re-evaluation of both the diagnostic and therapeutic roles of Ca disodium EDTA may be advisable.
Abstract: After its successful application to the treatment of acute Pb poisoning, Ca disodium EDTA came into routine clinical use for diagnosis and treatment of subacute and chronic Pb poisoning. Despite widespread use, few definitive conclusions have emerged about the sources of Pb mobilized by Ca disodium EDTA. Furthermore, the possibility that mobilized Pb may be redistributed has been suggested. The current studies indicate that the standard therapeutic protocol for Ca disodium EDTA has little impact on critical organs such as brain and liver and moreover, that diagnostic Ca disodium EDTA chelation may even increase the concentration of Pb in these tissues. After a 3 to 4 month exposure to Pb acetate in drinking water, different groups of rats received daily i.p. injections of saline (control), 75 or 150 mg/kg of Ca disodium EDTA for either 1, 2, 3, 4 or 5 days and were then sacrificed 24 hr after the final injection. Tissue analyses indicated that Pb was mobilized from bone and kidney and redistributed initially to both brain and liver. Levels in both brain and liver declined with subsequent Ca disodium EDTA injections, but no net loss from either tissue occurred over the 5-day treatment period despite a decline in blood Pb levels and a marked enhancement of urinary Pb excretion. These findings stress the need for further investigation of Ca disodium EDTAs effects and for parallel evaluation of alternate chelating agents, and suggest that a re-evaluation of both the diagnostic and therapeutic roles of Ca disodium EDTA may be advisable.

165 citations

Journal ArticleDOI
TL;DR: Comparison of biliary and fecal excretion rates indicates that arsenic and selenium undergo intestinal reabsorption, whereas thallium and zinc enter the feces also by non-biliary routes.

165 citations

Journal ArticleDOI
TL;DR: In situ dental amalgams can increase the level of mercury in expired air, and examined subjects with dental amalgAMS had higher pre-chewing mercury levels in their expired air than those without amalgams.
Abstract: The expired air of a group of 48 persons, 40 with and eight without dental amalgam restorations, was analyzed for its mercury content before and after chewing. Expired air samples were collected in polyethylene bags, and a known quantity of each was pumped into the mercury detector for measurement. The results showed that examined subjects with dental amalgams had higher pre-chewing mercury levels in their expired air than those without amalgams. After chewing, these levels were increased an average of 15.6-fold in the former and remained unchanged in the latter group. It was concluded that in situ dental amalgams can increase the level of mercury in expired air.

160 citations