scispace - formally typeset
Search or ask a question
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)

Content maybe subject to copyright    Report

Citations
More filters
Journal ArticleDOI
TL;DR: Based on the survey, it is recommended to detect contaminated areas and consider an educational plan for the exposed people to prevention of lead poisoning.
Abstract: Background and objective: Lead poisoning have been reported from many parts of the world. They are one of global clinical problem that effect all body organs and many deaths every year. This review was done to survey toxicological aspects of lead compounds Methods: The data bank used in this study is web of science, scopus, pubmed, pubmed central, SID. The keywords are Alzheimer�s Disease, medical plants, acetylcholine, antioxidant. Findings: Metallic lead is used industrial, organic lead eg., tetraethyl and tetramethyl lead in gasoline additives to prevent engine knock, and inorganic lead salts combined with other elements. Majority of absorptive lead through the respiratory and gastrointestinal systems. Lead compounds can lead to clinical manifestation in neurologic system, hematopoietic, kidneys, cardiovascular, reproduction, bones. There are tests available to diagnose poisoning by measuring lead in blood, urine, hair and fingernails. Patients of lead toxicity need to decontamination (GI tract irrigation), supportive cares, use traditional and new chelating agents to combination therapy, also antioxidants, vitamins, and nanoparticle. Conclusion: Based on the survey, it is recommended to detect contaminated areas and consider an educational plan for the exposed people to prevention of lead poisoning. © 2015, Babol University of Medical Sciences. All right reserved.

6 citations


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

  • ...New chelating agents: Succimer 2,3- dimercaptosuccinic acid (succimer, DMSA) has been used since 1950 as an antidote to lead poisoning in Russia, Japan and China (93)....

    [...]

  • ...New chelating agents: Succimer 2,3dimercaptosuccinic acid (succimer, DMSA) has been used since 1950 as an antidote to lead poisoning in Russia, Japan and China (93)....

    [...]

Dissertation
01 Jan 2017
TL;DR: This project aimed to investigate potential hyperthermic treatment of cancer cells in vitro by adopting nanomedicine principles, and found that cell death occurred predominantly via several apoptotic pathways, through increased fold expression changes in apoptotic markers.
Abstract: An estimated 12 million people worldwide are diagnosed with cancer every year, with around 17 million cancer-related deaths per year predicted by 2030 (Thun et al. 2010). Contemporary clinical treatments include surgery, chemotherapy and radiotherapy, however all vary in success and exhibit unpleasant side effects. Localised tumour hyperthermia is a moderately new cancer treatment envisaged by researchers, which exploits exclusive tumour vulnerabilities to specific temperature profiles (42-45°C) leading to cancer cell apoptosis, whilst normal tissue cells are relatively unaffected. Hyperthermia is therefore proposed as an alternative potential therapy for cancer, by delivering localised treatment to cancer cells, without the severe side effects associated with traditional therapies. This project aimed to investigate potential hyperthermic treatment of cancer cells in vitro by adopting nanomedicine principles. Inorganic nanoparticles, such as gold or iron oxide, are both capable of generating heat when appropriately stimulated, therefore both have been suggested as candidates for inducing localised tumour heating following their internalisation into cells. In this project, both gold (GNPs) and magnetic (mNPs) were individually assessed for their potential to deliver toxic thermal energy to bone cancer cells (MG63) and breast cancer cells (MCF-7). Studies were carried out both in standard 2D monolayer and in 3D tumour spheroids. When considering use in vivo, it is essential that both GNPs and mNPs are biocompatible, therefore initial studies characterised the cell viability and metabolic activity following incubation with the NPs. The NP internalisation was subsequently verified, prior to hyperthermic studies. Following hyperthermic treatment, both GNPs and mNPs were confirmed as inducing cancer cell death. Further studies were carried out using the GNPs, to identify the cell death pathways activated, where mitochondrial stress was evident following 2D culture tests. Gene and protein expression analysis indicated that cell death occurred predominantly via several apoptotic pathways, through increased fold expression changes in apoptotic markers. Interestingly, cell protective mechanisms were simultaneously switched on, as cells were also observed to exhibit thermotolerance with a number of heat shock proteins (Hsps) being substantially increased during hyperthermic treatments.

5 citations


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

  • ...Although not conventionally used, DMSA is a well-known molecule, considered non-toxicand orally administrated as a chelating agent to remove heavy metals from an organism representing its biocompatibility (M. P. Garcia et al. 2005; Miller 1998)....

    [...]

Journal ArticleDOI
TL;DR: In this article , the authors present an overview of conventional chelating agents and the potential role of flavonoids and stilbenoids in ameliorating arsenic toxicity, which may provide a roadmap for identifying novel prophylactic/therapeutic strategies for managing arsenic toxicity.

3 citations

04 Dec 2008
TL;DR: The results showed that the concomitant and acute exposure to HgCl2 and therapeutic agents tested presented toxic effects, and that the preventive therapy with diphenyl diselenide (PhSe)2 was effective in protecting against immunological and hematological alterations induced by subchronic HGCl2 exposure.
Abstract: O mercurio (Hg) e um elemento ainda sem funcao fisiologica no organismo humano, sendo toxico aos seres vivos. Este metal possui ampla aplicacao na industria sendo, portanto, bastante importante na exposicao ocupacional e ambiental. A toxicidade do mercurio depende da forma deste metal e pode afetar inumeros orgaos, tais como o cerebro, os rins e o figado e, ainda, causar alteracoes hematologicas e imunologicas. O estresse oxidativo parece estar envolvido na toxicidade induzida pelo mercurio, uma vez que este metal pode causar um aumento na producao de especies reativas de oxigenio (EROs) e disturbios nos sistemas de defesa antioxidante enzimaticos e nao-enzimaticos. Desta forma, alem das terapias convencionais por meio de agentes quelantes, terapias utilizando agentes antioxidantes sao testadas na tentativa de reduzir os efeitos toxicos deste metal. Considerando que o composto disseleneto de difenila (PhSe)2 possui inumeras propriedades farmacologicas, dentre as quais destaca-se a sua acao antioxidante, o nosso objetivo foi verificar o efeito deste composto em diferentes modelos de exposicao ao cloreto de mercurio (HgCl2) em camundongos. As utilizacoes de outro agente antioxidante, a N-acetilcisteina (NAC), e de um agente quelante de referencia, o acido 2,3-dimercapto-1-propanosulfonico (DMPS), tambem foram avaliadas. Os resultados obtidos demonstraram que quando o HgCl2 foi administrado de forma aguda e a utilizacao dos agentes terapeuticos testados ocorreu de forma concomitante, efeitos toxicos decorrentes destas interacoes foram observados. De fato, a administracao de NAC e DMPS, em animais expostos ao HgCl2, causou toxicidade renal nos camundongos, o que foi evidenciado atraves de um aumento nos niveis de ureia e creatinina e atraves da reducao na atividade da enzima Na+, K+-ATPase renal. Esta toxicidade foi devida a uma possivel formacao de complexos toxicos entre o metal e estes agentes. A administracao de (PhSe)2 causou 100% de morte nos animais expostos ao HgCl2. Os efeitos toxicos decorrentes desta associacao afetam o tecido hepatico e, principalmente, o tecido renal. O dano hepatico foi caracterizado pelo aumento nos niveis de peroxidacao lipidica e reducao na atividade da enzima catalase nos animais do grupo HgCl2 + (PhSe)2. O dano renal foi caracterizado atraves de marcadores bioquimicos no plasma e na urina dos camundongos. Alem disso, os camundongos expostos a associacao entre o HgCl2 e o (PhSe)2 apresentaram inibicoes na atividade das enzimas glutationa S-transferase (GST) e Na+, K+-ATPase renal. O dano oxidativo no tecido renal foi evidenciado atraves do aumento nos niveis de peroxidacao lipidica e aumento na concentracao de acido ascorbico nos camundongos expostos ao HgCl2 e ao (PhSe)2, de forma concomitante. Elevados valores de hemoglobina e hematocrito tambem foram observados nos camundongos do grupo HgCl2 + (PhSe)2 e o dano renal parece estar envolvido neste efeito. A formacao de um complexo entre o HgCl2 e o (PhSe)2, o qual apresenta atividades pro-oxidantes, e a hipotese mais provavel para…

2 citations


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

  • ...O acúmulo de metais pesados no organismo humano representa um risco significativo para a saúde, levando a uma grande variedade de patologias, como a anemia, o câncer, a insuficiência renal crônica, a hipertensão, a gota, a infertilidade masculina, a gengivite, entre outros (Miller, 1998)....

    [...]

  • ...Estes metais são amplamente encontrados em nosso ambiente e os seres humanos são expostos a tais metais a partir de inúmeras fontes, incluindo o ar, a água, o solo e os alimentos (Miller, 1998)....

    [...]

01 Jan 2011
TL;DR: Another MRI-based technique for assessing induction of an immune response was developed, based on the simple observation that lymph nodesdraining the injection site became enlarged, and the heightened sensitivity and specificity improved the threshold of cancer detection on previous studies performed at 1.5 T.
Abstract: Magnetic nanoparticles are effective in a range of biomedical applications including magneticresonance imaging (MRI) contrast enhancement. The efficacy of nanoparticles ascontrast agents depends mainly on the surface chemistry and magnetic properties of theparticles, with a large magnetic moment inducing efficient transverse (T₂) relaxation ofprotons. This results in improved negative enhancement of MRI contrast on T₂ weightedsequences. Iron oxide nanoparticles (FeOx NPs) have been used in MRI for 20 years andare the only commercially available T₂ contrast agents. A significantly larger magneticmoment can potentially be achieved with iron nanoparticles (Fe NPs), but developmenthas been hampered by difficulty in preparing stable particles. In this study, stable Fe NPwere prepared by a novel, simple, synthesis and compared with FeOx NP as T₂ contrastagents in a range of MRI-based biomedical applications.The effectiveness of Fe NPs versus FeOx NPs to negatively enhance MRI contrast onT₂ weighted sequences was first examined in vitro. The Fe NPs and FeOx NPs werecharacterised by electron microscopy and found to be of similar size (16nm). The Fe NPspossessed a core of highly magnetic α-Fe inside a 3nm shell of FeOx of the same crystalstructure as the pure FeOx NPs. Both types of NP were coated with the same molecule,DMSA, to produce aqueous dispersions with similar hydrodynamic particle sizes andpharmacokinetics. When dispersed in gels and examined by MRI, the Fe NPs were foundto produce more than twice the amount of T₂ contrast change per unit concentrationrelative to FeOx NPs. When cells were labelled in vitro, Fe NPs produced greater T₂contrast enhancement in all cell types tested, whilst there was no significant difference in the uptake of iron or the cytotoxicity between cells labelled with Fe or FeOx NPs.To assess the clinical applicability of the nanoparticles in vivo, FeOx NPs and Fe NPswere administered to mice and MRI experiments were performed at 1.5 T. Contrast effectsof the NPs were examined in the liver, spleen and lymph nodes, as tissues in theseorgans are rich in phagocytic cells and have a strong tendency to take up circulatingNPs. In all three organs studied, the Fe NPs produced noticeably darker contrast thanthe FeOx NPs, providing twice the contrast improvement.One of the most intensely researched applications of magnetic nanoparticles in MRI is improving detection of cancer in the lymph nodes. To model the size and NP uptake ofsmall lymph node metastases in humans, a mouse model was developed by injecting 4T1breast cancer cells directly into the mouse spleen. Analysis of mice bearing 4T1 tumoursperformed at 1.5 T showed that Fe NPs produced better contrast than FeOx NPs andimproved the detection of small tumours in the spleen as determined by two blindedradiologists. Indeed, the heightened sensitivity and specificity improved the threshold ofcancer detection on previous studies performed at 1.5 T.It was then examined whether the improved T₂ contrast could enable new MRI applicationsin vivo. A novel assay to detect induced immune responses following dendriticcell-based vaccination using MRI was developed. By tracking cells labelled with ironnanoparticles, a difference in contrast could be detected between nave mice and thosethat had developed a strong immune response after vaccination. This assay only reachedstatistical significance with Fe NPs and not with FeOx NPs.As a consequence of these studies, another MRI-based technique for assessing inductionof an immune response was developed, based on the simple observation that lymph nodesdraining the injection site became enlarged. This enlargement was seen as early as 12 hours after vaccination and was caused by a cellular in filtrate dominated by lymphoidcells. In experiments where vaccination was performed multiple times using different tumoursas a source of antigen, incremental increases in lymph node size were detectableby MRI, which was shown to be a highly antigen-specific response. In the vaccine modelstudied, the increase in lymph node size was associated with protection from a tumour challenge. Thus, Fe NPs produce a significant improvement of T₂ contrast over FeOx NPs in a rangeof applications without any differences found in uptake or cytotoxicity. These findingsare substantial enough to justify further investigations into the application of Fe NPs ina variety of clinical settings.

2 citations

References
More filters
Journal ArticleDOI
TL;DR: This article reviews the pharmacological properties and the uses of two important antidotes for heavy metal poisoning, DMSA and DMPS, water soluble chemical analogs of dimercaprol, which have less toxicity, greater water solubility, and lim­ ited lipid solubilities, and are effective when given orally.
Abstract: This article reviews the pharmacological properties and the uses of two important antidotes for heavy metal poisoning. Meso-dimercaptosuccinic acid (DMSA) and 2,3-dimercapto-l-propanesulfonic acid, Na salt (DMPS) are relatively new antidotes-new, that is, to the western world. Although DMSA was introduced originally by Friedheim et al (1) to increase uptake of antimony during schistosomiasis therapy, Liang et al (77) at Shanghai in 1957 were the first to report its effectiveness as an antidote for heavy metal poisoning. The synthesis and some of the metal binding properties of DMPS were reported in 1956 by Petrunkin from Kiev (3). Shortly thereaf­ ter, DMPS became an official drug in the Soviet Union, where it is known as Unithiol (4). Between 1956 and 1975, DMSA and DMPS were studied extensively, at both the basic science and clinical levels, in the People's Republic of China, the Soviet Union, and Japan. Some of these investigations have been cited and can be found in an earlier review (5). In the USA and western Europe, however, these two compounds received very little attention until recently. A paper by Friedheim & Corvi (6) in 1975, dealing with DMSA for the treatment of mercury poisoning, and the recent production and availability of DMPS from Heyl & Co., Berlin, stimulated investigators to "rediscover" and study these two metal-binding agents. DMSA and DMPS are water soluble chemical analogs of dimercaprol (British Anti-Lewisite, BAL). In contrast to BAL, they have less toxicity, greater water solubility, and lim­ ited lipid solubility, and are effective when given orally.

309 citations


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

  • ...DMSA has been shown in recent studies to be a safe and effective chelator of lead, reducing blood levels significantly.(1,34,35) At a dose of 10 mg/kg for five days in adult males, DMSA lowered blood lead levels 35....

    [...]

  • ...DMSA was subsequently studied for twenty years in the People’s Republic of China, Japan, and Russia before scientists in Europe and the United States “discovered” the substance and its potential usefulness in the mid-1970s.(1) DMSA is a dithiol (containing two sulfhydryl, or S-H, groups) and an analogue of dimercaprol (BAL, British Anti-Lewisite), a lipid-soluble compound also used for metal chelation (see Figure 1)....

    [...]

Journal ArticleDOI
TL;DR: It has been discovered that microtubules are destroyed by this form of mercury and this effect may explain the inhibition of cell division and cell migration, processes that occur only in the developmental stages, and other hypotheses will stimulate considerable experimental challenges in the future.
Abstract: The nervous system is the principal target for a number of metals. Inorganic compounds of aluminum, arsenic, lead, lithium, manganese, mercury, and thallium are well known for their neurological and behavioral effects in humans. The alkyl derivatives of certain metals--lead, mercury and tin--are specially neurotoxic. Concern over human exposure and in some cases, outbreaks of poisoning, have stimulated research into the toxic action of these metals. A number of interesting hypotheses have been proposed for the mechanism of lead toxicity on the nervous system. Lead is known to be a potent inhibitor of heme synthesis. A reduction in heme-containing enzymes could compromise energy metabolism. Lead may affect brain function by interference with neurotransmitters such as gamma-amino-isobutyric acid. There is mounting evidence that lead interferes with membrane transport and binding of calcium ions. Methylmercury produces focal damage to specific areas in the adult brain. One hypothesis proposes that certain cells are susceptible because they cannot repair the initial damage to the protein sythesis machinery. The developing nervous system is especially susceptible to damage by methylmercury. It has been discovered that microtubules are destroyed by this form of mercury and this effect may explain the inhibition of cell division and cell migration, processes that occur only in the developmental stages. These and other hypotheses will stimulate considerable experimental challenges in the future.

196 citations


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

  • ...Methyl mercury also easily crosses the blood-brain barrier and the placenta.(7) Inorganic and methyl mercury have a high affinity for sulfhydryls, reacting intracellularly with the sulfhydryl group on glutathione and cysteine, and histidine residues in proteins, and allowing transport out of the cell....

    [...]

  • ...After lead is absorbed in the human body, it reacts with thiol (sulfhydryl) groups on peptides and proteins, inhibiting enzymes involved in heme synthesis and interfering with normal neurotransmitter functions.(7) This natural reaction with thiols is also the body’s method of eliminating lead, especially from the liver....

    [...]

Journal ArticleDOI
TL;DR: Analysis of the data from the questionnaires indicated that little or no exogenous exposure to mercury occurred among the two groups.
Abstract: Mercury levels in blood and in mouth air before and after chewing were measured in 47 persons with ana 14 persons without dental amalgam restorations. Questionnaires relating to exogenous sources of mercury exposure were administered to both groups. Differences in the mouth air mercury levels before and after chewing were statistically significant in the group with amalgams, but not in the group without amalgams. Analysis of the data from the questionnaires indicated that little or no exogenous exposure to mercury occurred among the two groups. Blood mercury concentrations were positively correlated with the number and surface area of amalgam restorations and were significantly lower in the group without dental amalgams.

194 citations

Journal ArticleDOI
TL;DR: Animal and human experiments demonstrate that the uptake, tissue distribution, and excretion of amalgam Hg is significant, and that dental amalgam is the major contributing source to Hg body burden in humans.
Abstract: For more than 160 years dentistry has used silver amalgam, which contains approximately 50% Hg metal, as the preferred tooth filling material. During the past decade medical research has demonstrated that this Hg is continuously released as vapor into mouth air; then it is inhaled, absorbed into body tissues, oxidized to ionic Hg, and finally covalently bound to cell proteins. Animal and human experiments demonstrate that the uptake, tissue distribution, and excretion of amalgam Hg is significant, and that dental amalgam is the major contributing source to Hg body burden in humans. Current research on the pathophysiological effects of amalgam Hg has focused upon the immune system, renal system, oral and intestinal bacteria, reproductive system, and the central nervous system. Research evidence does not support the notion of amalgam safety.

178 citations

Journal ArticleDOI
TL;DR: Results suggest that lead-induced oxidative stress in vivo can be mitigated by pharmacologic interventions, which encompass both chelating as well as thiol-mediated antioxidant functions.

172 citations