Strategies for safe and effective therapeutic measures for chronic arsenic and lead poisoning.
01 Jan 2005-Journal of Occupational Health (Japan Society for Occupational Health)-Vol. 47, Iss: 1, pp 1-21
TL;DR: The present review article attempts to provide update information about the current strategies being adopted for a safe, effective and specific treatment for two major toxic metals or metalloid.
Abstract: Exposure to toxic metals remains a widespread occupational and environmental problem in world. There have been a number of reports in the recent past suggesting an incidence of childhood lead poisoning and chronic arsenic poisoning due to contaminated drinking water in many areas of West Bengal in India and Bangladesh has become a national calamity. Low level metal exposure in humans is caused by air, food and water intake. Lead and arsenic generally interferes with a number of body functions such as the central nervous system (CNS), the haematopoietic system, liver and kidneys. Over the past few decades there has been growing awareness and concern that the toxic biochemical and functional effects are occurring at a lower level of metal exposure than those that produce overt clinical and pathological signs and symptoms. Despite many years of research, we are still far from an effective treatment of chronic plumbism and arsenicosis. Medical treatment of acute and chronic lead and arsenic toxicity is furnished by chelating agents. Chelating agents are organic compounds capable of linking together metal ions to form complex ring-like structures called chelates. They have been used clinically as antidotes for acute and chronic poisoning. 2, 3-dimercaprol (BAL) has long been the mainstay of chelation therapy for lead or arsenic poisoning. Meso 2, 3, -dimercaptosuccinic acid (DMSA) has been tried successfully in animals as well as in a few cases of human lead and arsenic poisoning. DMSA could be a safe and effective method for treating lead or arsenic poisoning, but one of the major disadvantages of chelation with DMSA has been its inability to remove lead from the intracellular sites because of its lipophobic nature. Further, it does not provide protection in terms of clinical/ biochemical recovery. A new trend in chelation therapy is to use combined treatment. This includes the use of structurally different chelators or a combination of an adjuvant and a chelator to provide better clinical/biochemical recovery in addition to lead mobilization. The present review article attempts to provide update information about the current strategies being adopted for a safe, effective and specific treatment for two major toxic metals or metalloid.
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TL;DR: An overview of redox and non-redox metal-induced formation of free radicals and the role of oxidative stress in toxic action of metals is provided.
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TL;DR: A comprehensive account of recent updates describing health effects of lead exposure, relevant biomarkers and mechanisms involved in lead toxicity, and updates the readers about recent advances in chelation therapy and newer therapeutic strategies, like nanoencapsulation, to treat lead induced toxic manifestations are provided.
Abstract: Lead poisoning has been recognized as a major public health risk, particularly in developing countries. Though various occupational and public health measures have been undertaken in order to control lead exposure, cases of lead poisoning are still reported. Exposure to lead produces various deleterious effects on the hematopoietic, renal, reproductive and central nervous system, mainly through increased oxidative stress. These alterations play a prominent role in disease manifestations. Modulation of cellular thiols for protection against reactive oxygen species (ROS) has been used as a therapeutic strategy against lead poisoning. N-acetylcysteine, α-lipoic acid, vitamin E, quercetin and a few herbal extracts show prophylaxis against the majority of lead mediated injury in both in vitro and in vivo studies. This review provides a comprehensive account of recent updates describing health effects of lead exposure, relevant biomarkers and mechanisms involved in lead toxicity. It also updates the readers about recent advances in chelation therapy and newer therapeutic strategies, like nanoencapsulation, to treat lead induced toxic manifestations.
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Journal Article•
TL;DR: A comprehensive account of recent developments in the research on heavy metal poisoning particularly the role of oxidative stress/free radicals in the toxic manifestation is attempted, an update about the recent strategies for the treatment with chelating agents and a possible beneficial role of antioxidants supplementation to achieve the optimum effects are attempted.
Abstract: Exposure to heavy metals is a common phenomenon due to their environmental pervasiveness. Metal intoxication particularly neurotoxicity, genotoxicity, or carcinogenicity is widely known. This review summarizes our current understanding about the mechanism by which metalloids or heavy metals (particularly arsenic, lead, cadmium and mercury) induce their toxic effects. The unifying factor in determining toxicity and carcinogenicity for all these metals is the generation of reactive oxygen and nitrogen species. The toxic manifestations of these metals are caused primarily due to imbalance between pro-oxidant and antioxidant homeostasis which is termed as oxidative stress. Besides these metals have high affinity for thiol groups containing enzymes and proteins, which are responsible for normal cellular defense mechanism. Long term exposure to these metals could lead to apoptosis. Signaling components affected by metals include growth factor receptors, G-proteins, MAP kinases and transcription factors. Chelation therapy with chelating agents like calcium disodium ethylenediamine tetra acetic acid (CaNa(2)EDTA), British Anti Lewisite (BAL), sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), meso 2,3-dimercaptosuccinic acid (DMSA) etc., is considered to be the best known treatment against metal poisoning. Despite many years of research we are still far away from effective treatment against toxicity caused due to exposure to heavy metals/metalloids. The treatment with these chelating agents is compromised with number of serious side-effects. Studies show that supplementation of antioxidants along-with a chelating agent prove to be a better treatment regimen than monotherapy with chelating agents. This review attempts a comprehensive account of recent developments in the research on heavy metal poisoning particularly the role of oxidative stress/free radicals in the toxic manifestation, an update about the recent strategies for the treatment with chelating agents and a possible beneficial role of antioxidants supplementation to achieve the optimum effects. We have selected only arsenic, lead, mercury and cadmium for this article keeping in view current concerns and literature available.
840 citations
TL;DR: A deep understanding of the mechanisms involved in eliciting heavy metals toxicity is provided in order to highlight the necessity for development of strategies to decrease exposure to these metals, as well as to identify substances that contribute significantly to overcome their hazardous effects within the body of living organisms.
Abstract: Heavy metals, which have widespread environmental distribution and originate from natural and anthropogenic sources, are common environmental pollutants. In recent decades, their contamination has increased dramatically because of continuous discharge in sewage and untreated industrial effluents. Because they are non-degradable, they persist in the environment; accordingly, they have received a great deal of attention owing to their potential health and environmental risks. Although the toxic effects of metals depend on the forms and routes of exposure, interruptions of intracellular homeostasis include damage to lipids, proteins, enzymes and DNA via the production of free radicals. Following exposure to heavy metals, their metabolism and subsequent excretion from the body depends on the presence of antioxidants (glutathione, α-tocopherol, ascorbate, etc.) associated with the quenching of free radicals by suspending the activity of enzymes (catalase, peroxidase, and superoxide dismutase). Therefore, this review was written to provide a deep understanding of the mechanisms involved in eliciting their toxicity in order to highlight the necessity for development of strategies to decrease exposure to these metals, as well as to identify substances that contribute significantly to overcome their hazardous effects within the body of living organisms.
770 citations
Cites background from "Strategies for safe and effective t..."
...Besides being toxic in itself at higher concentrations, it has been found to enhance the toxicity imposed by Pb [218]....
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...Along with, Se administration was found to have a positive effect in reducing the Pb and As toxicities through increased production of Selenoproteins, competition at key enzymes and through formation of inert Se–metal complexes [218]....
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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
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