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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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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729 citations
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
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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TL;DR: The combination of a bone lead mobilizer and a soft tissue depleter such as meso-2,3-dimercaptosuccinic acid and DMSA was investigated for its efficacy to enhance the excretion of lead, to reduce its body burden, and to reverse certain lead-induced biochemical alterations by either of them alone in rats.
Abstract: The combination of a bone lead mobilizer, viz., CaNa2EDTA, and a soft tissue depleter such as meso-2,3-dimercaptosuccinic acid (DMSA) or the sodium salt of 2,3-dimercapto-1-propane-sulfonic acid (DMPS) was investigated for its efficacy to enhance the excretion of lead, to reduce its body burden, and to reverse certain lead-induced biochemical alterations by either of them alone in rats. The administration of CaNa2EDTA or DMSA was more effective than that of DMPS, and the combination of CaNa2EDTA and DMSA was more efficient than that of CaNa2EDTA and DMPS or the individual chelators in enhancing urinary/fecal excretion of lead, in reducing hepatic, renal, and femur concentration of lead, and in restoring lead-induced inhibition of blood delta-aminolevulinic acid dehydratase and increase in blood zinc protoporphyrin and urinary delta-aminolevulinic acid levels. The brain lead was depleted by DMSA only, but the combined chelation failed to improve upon the ability of DMSA. However, chelation therapy increased diuresis and tissue depletion of zinc.
27 citations
TL;DR: It seems safe to conclude that no health-related problems from Hg are to be expected from amalgam fillings, according toiological monitoring of mercury in blood, urine and hair.
25 citations
Journal Article•
TL;DR: In dogs with naturally acquired lead poisoning, succimer administered orally for 10 days effectively reduced blood lead concentrations and eliminated clinical signs of lead poisoning.
Abstract: OBJECTIVE To determine whether succimer (meso-2,3-dimercaptosuccinic acid) would be effective in reducing blood lead concentration in dogs with naturally acquired lead poisoning and whether treated dogs would develop clinically important adverse effects. DESIGN Prospective case series. ANIMALS 13 dogs with moderate-to-high blood lead concentrations (39 to 120 micrograms/dl) and clinical signs of lead poisoning. PROCEDURE Dogs were treated with succimer (10 mg/kg of body weight, PO, q 8 h) for 10 days. Blood and urine samples were analyzed for lead concentration before, during, and after treatment with succimer. RESULTS Mean blood lead concentrations on days 0, 3, 7, and 20 were 70.6, 32.7, 16.8, and 27.6 micrograms/dl, respectively. Mean blood lead concentrations decreased 53.6, 76.2, and 60.9% from pretreatment value on days 3, 7, and 20, respectively. Mean urine lead concentrations on days 0, 3, 7, and 20 were 70.0, 485.4, 254.3, and 28.3 micrograms/dl, respectively. CLINICAL IMPLICATIONS In dogs with naturally acquired lead poisoning, succimer administered orally for 10 days effectively reduced blood lead concentrations and eliminated clinical signs of lead poisoning.
23 citations
TL;DR: Oral administration of DMSA and DMPS were more efficient than parenteral administration in reducing whole-body retention and organ deposition of orally administered mercuric chloride, most likely due to the prevention of intestinal uptake of mercury.
Abstract: Acute toxicity and the disposition of inorganic mercury depends on the route of exposure. Most previous studies on effect of chelators on inorganic mercury toxicity and toxicokinetics employed pare...
21 citations
Journal Article•
TL;DR: The results showed great differences between the polished amalgams stored in air and amalgams corroded in artificial saliva, and single composition types released more mercury than conventional and dispersed ones.
Abstract: The aim of this investigation was to examine in vitro the rate of mercury vapor from different types of dental amalgams. Amalgam surfaces of three different states were used, polished, oxidized and corroded. The influence of temperature, tooth brushing and water on the specimens was also examined. The results showed great differences between the polished amalgams stored in air and amalgams corroded in artificial saliva. Single composition types released more mercury than conventional and dispersed ones. Higher temperature raised and water lowered the vapor rates. When the surfaces of the amalgams were brushed with a tooth paste, an instant increase of mercury vapor occurred.
18 citations