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: It is concluded that hair may be used as an indicator of internal uptake of mercury provided that it was not externally exposed to mercury vapour.
43 citations
TL;DR: Eight essential metals were detected at considerable concentrations in hepatic bile and urine collected simultaneously from three Japanese individuals, and the supplementation of these metals should occur during treatment of diseases accompanied by loss of hepatics bile.
Abstract: Fifteen metals (lead, cadmium, arsenic, inorganic mercury, organic mercury, iron, manganese, magnesium, chromium, zinc, copper, nickel, cobalt, tin, and aluminum) were determined in the hepatic bile and urine collected simultaneously from three Japanese individuals (2 males, 1 female). The presence of these metals was classified as follows: (1) hepatic biliary concentrations were higher than urinary concentrations (lead, arsenic, and iron); (2) urinary concentrations were higher than hepatic biliary concentrations (cadmium, inorganic mercury, tin, cobalt, magnesium, chromium, copper, zinc, and nickel); (3) hepatic biliary concentrations were almost equal to urinary concentrations (manganese and organic mercury); and (4) relationship between hepatic biliary and urinary concentrations changed occasionally (aluminum). Eight essential metals (iron, manganese, magnesium, zinc, chromium, copper, nickel, and cobalt) were detected at considerable concentrations in hepatic bile. Accounting for the daily f...
43 citations
Journal Article•
TL;DR: An assay for the determination of DMSA has been developed that indicates that DMSA is in disulfide linkage with plasma proteins and/or non-protein sulfhydryl compounds, and most of the DMSA in the plasma was found to be bound to plasma proteins, mainly albumin.
Abstract: meso-2,3-Dimercaptosuccinic acid (DMSA) is orally effective for the treatment of chronic lead intoxication in humans. Earlier studies have shown that the majority of DMSA, given p.o. to normal humans, is excreted in the urine as mixed disulfides with L-cysteine. We have developed an assay for the determination of DMSA that has made possible the determination of the form of DMSA in blood and plasma. After p.o. administration of 10 mg DMSA/kg to four normal young men, no unaltered DMSA (unaltered DMSA is the unbound, parent compound; total DMSA consists of unaltered DMSA plus oxidized (disulfide) DMSA and is determined after reduction with dithiothreitol) was found in the blood over an 8-hr period. Only after treatment of blood or plasma with the disulfide-reducing agent, dithiothreitol, was DMSA detected. This indicates that DMSA is in disulfide linkage with plasma proteins and/or non-protein sulfhydryl compounds. Most of the DMSA in the plasma (92-95%) was found to be bound to plasma proteins, mainly albumin. The remaining DMSA may be bound to small molecular weight (less than 10,000 MW) nonprotein sulfhydryl compounds such as cysteine. Plasma protein appears to serve as a depot and reservoir of DMSA, which can exchange for cysteine. The urinary excretion of unaltered DMSA and DMSA mixed disulfides with L-cysteine suggests that this exchange takes place at the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)
39 citations
TL;DR: The results suggest that individuals with many amalgam restorations, i.e., more than 36 restored surfaces, absorb 10-12 micrograms Hg/day.
Abstract: .Mean values were HgB = 24.S nmoll1. HgU _ 17,5 nmolll and HgAir = O.S j.4glm', HgU correlated with HgAir. and both HgU and HgAir with the number of amalgam restoralions, amalgam restored surfaces and amalgam restored occlusal surfaces. 11gB sho,",'ed poor correlalion to HgU and HgAir and the presence of amalgam reslorations . A differenlialion of the mercury absorplion due lO exposure from dental amalgams and from the dietary intake, necessitates measurements of both organic and inorganic mercury in the pla,ma, and in the erYlhrocytes. The results suggesl that individuub with muny umalgam restoration:;, i.e., more lhan 36 restored surfaces, absorb 10 12 ~!g l'lglday. In order to estimate the impact of the exposure to mercury in the cnvironment on general health it is necessary to identify. characterize and quantify all contributing SOUf(;es. One potential source have been shown to be the degradation of dcntal restorations made from amalgam (Brune & Evje 1985). Dental amalgams consi~t of approximately 45-5(),~'O
38 citations
TL;DR: The DMS treatment, as well as DMS + spironolactone in combination, could protect against kidney damage following injection of 30 mumol HgCl2/kg, and was essentially nontoxic.
Abstract: The distribution and excretion of mercury were studied in mice given a single injection of HgCl2 with or without chelation treatment. DMS (2,3-dimercaptosuccinic acid) given intravenously (0.5 mmol SH/kg) to mice 24 h after the mercury injection reduced the kidney Hg level significantly, while NAPA (N-acetyl-DL-penicillamine) and BAL (2,3-dimercaptopropanol) did not. The effectivity of DMS to remove Hg from kidneys was comparable to that of BAL-sulph (2,3-dimercaptopropane-1-sulfonate), irrespective of whether these chelating agents were given orally or intravenously. Immediate chelation treatment with DMS or mercaptodextran reduced the renal Hg level to about 50% of control levels, as measured 3 d after the treatment. Combination of DMS with immediate intraperitoneal treatment with spironolactone was even more effective in reducing the renal levels, and acted both by increasing the fecal and urinary excretion. The DMS treatment, as well as DMS ± spironolactone in combination, could protect agains...
36 citations