Journal Article•
Molecular Interactions with Mercury in the Kidney
01 Mar 2000-Pharmacological Reviews (American Society for Pharmacology and Experimental Therapeutics)-Vol. 52, Iss: 1, pp 113-144
TL;DR: This review provides an update on the current body of knowledge regarding the molecular interactions that occur between mercury and various thiol-containing molecules with respect to the mechanisms involved in the renal cellular uptake, accumulation, elimination, and toxicity of mercury.
Abstract: Mercury is unique among the heavy metals in that it can exist in several physical and chemical forms, including elemental mercury, which is a liquid at room temperature. All forms of mercury have toxic effects in a number of organs, especially in the kidneys. Within the kidney, the pars recta of the proximal tubule is the most vulnerable segment of the nephron to the toxic effects of mercury. The biological and toxicological activity of mercurous and mercuric ions in the kidney can be defined largely by the molecular interactions that occur at critical nucleophilic sites in and around target cells. Because of the high bonding affinity between mercury and sulfur, there is particular interest in the interactions that occur between mercuric ions and the thiol group(s) of proteins, peptides and amino acids. Molecular interactions with sulfhydryl groups in molecules of albumin, metallothionein, glutathione, and cysteine have been implicated in mechanisms involved in the proximal tubular uptake, accumulation, transport, and toxicity of mercuric ions. In addition, the susceptibility of target cells in the kidneys to the injurious effects of mercury is modified by a number of intracellular and extracellular factors relating to several thiol-containing molecules. These very factors are the theoretical basis for most of the currently employed therapeutic strategies. This review provides an update on the current body of knowledge regarding the molecular interactions that occur between mercury and various thiol-containing molecules with respect to the mechanisms involved in the renal cellular uptake, accumulation, elimination, and toxicity of mercury.
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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
TL;DR: This review will present the established and putative roles of molecular and ionic mimicry in the transport of mercury, cadmium, lead, arsenic, selenium, and selected oxyanions in target organs and tissues.
664 citations
Cites background from "Molecular Interactions with Mercury..."
...This indicates that Cd2+ is extracted from the blood very rapidly by the liver and other organs and tissues (Zalups, 2000b)....
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...For example, as much as 60% of a nontoxic dose of Cd2+ (5 Amol/kg) has been shown to accumulate in the liver of rats within 1 h after intravenous administration (Zalups, 2000b)....
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...Studies in rats show that when GSH or Cys are simultaneously injected (intravenously) with Cd2+, the renal uptake of Cd2+ increases significantly (Zalups, 2000b)....
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...Yet, many studies have proven that these toxic metals do indeed gain entry into various target cells (for reviews, see Clarkson, 1993; Ballatori, 2002; Zalups, 2000a; Zalups and Ahmad, 2003)....
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...It has been proposed that g-glutamyltransferase and cysteinylglycinase, which are present in abundance on the luminal (brush-border) plasma membrane of proximal tubular cells, act upon GSH S-conjugates of CH3Hg + (CH3Hg-S-G) to yield CH3Hg-S-Cys (reviewed by Zalups, 2000a)....
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TL;DR: Both the color and the fluorescence emission changes of the DNA-functioned gold nanoparticles generated by Hg2+ are the results of the metal-induced formation of dsDNA and subsequent formation of nanoparticle aggregates.
Abstract: An approach for visual and fluorescent sensing of Hg2+ in aqueous solution is presented. This method is based on the Hg2+-induced conformational change of a thymine (T)-rich single-stranded DNA (ssDNA) and the difference in electrostatic affinity between ssDNA and double-stranded (dsDNA) with gold nanoparticles. The dye-tagged ssDNA containing T−T mismatched sequences was chosen as Hg2+ acceptor. At high ionic strength, introduction of the ssDNA to a colloidal solution of the aggregates of gold nanoparticles results in color change, from blue-gray to red of the solution, and the fluorescence quenching of the dye. Binding of Hg2+ with the ssDNA forms the double-stranded structure. This formation of dsDNA reduces the capability to stabilize bare nanoparticles against salt-induced aggregation, remaining a blue-gray in the color of the solution, but fluorescence signal enhancement compared with that without Hg2+. With the optimum conditions described, the system exhibits a dynamic response range for Hg2+ from...
467 citations
TL;DR: This critical review describes the basic fabrication principles, the configuration designs of SPEs and the hybrid analytical techniques based on SPEs, including the determination of organic compounds, heavy metals and gas pollutants over the past 3 years.
426 citations
References
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Book•
01 Jan 1969
TL;DR: The toxicology of commercial products and its applications are studied in the context of food safety, cosmetics and personal care products.
Abstract: Clinical toxicology of commercial products , Clinical toxicology of commercial products , کتابخانه دیجیتال جندی شاپور اهواز
1,062 citations
01 Mar 1999
TL;DR: This edition supersedes any previously released draft or final profile and is a three-volume set of recommendations for on-scene and hospital medical management of patients exposed during a hazardous materials incident.
Abstract: DISCLAIMER The use of company or product name(s) is for identification only and does not imply endorsement by the Agency for Toxic Substances and Disease Registry. A Toxicological Profile for Mercury–Draft for Public Comment was released in September 1997. This edition supersedes any previously released draft or final profile. Toxicological profiles are revised and republished as necessary, but no less than once every three years. For information regarding the update status of previously released profiles, contact ATSDR at: Toxicological Profiles are a unique compilation of toxicological information on a given hazardous substance. Each profile reflects a comprehensive and extensive evaluation, summary, and interpretation of available toxicologic and epidemiologic information on a substance. Health care providers treating patients potentially exposed to hazardous substances will find the following information helpful for fast answers to often-asked questions. Chapter 1: Public Health Statement: The Public Health Statement can be a useful tool for educating patients about possible exposure to a hazardous substance. It explains a substance's relevant toxicologic properties in a nontechnical, question-and-answer format, and it includes a review of the general health effects observed following exposure. Chapter 2: Health Effects: Specific health effects of a given hazardous compound are reported by route of exposure, by type of health effect (death, systemic, immunologic, reproductive), and by length of exposure (acute, intermediate, and chronic). In addition, both human and animal studies are reported in this section. NOTE: Not all health effects reported in this section are necessarily observed in the clinical setting. Please refer to the Public Health Statement to identify general health effects observed following exposure. The following additional material can be ordered through the ATSDR Information Center: Case Studies in Environmental Medicine: Taking an Exposure History—The importance of taking an exposure history and how to conduct one are described, and an example of a thorough exposure history is provided. Other case studies of interest include Reproductive and Developmental Hazards; Skin Lesions and Environmental Exposures; Cholinesterase-Inhibiting Pesticide Toxicity; and numerous chemical-specific case studies. viii MERCURY Managing Hazardous Materials Incidents is a three-volume set of recommendations for on-scene (prehospital) and hospital medical management of patients exposed during a hazardous materials incident. Volumes I and II are planning guides to assist first responders and hospital emergency department personnel in planning for incidents that involve hazardous materials. Volume III—Medical Management Guidelines for Acute Chemical Exposures—is a guide for health care professionals treating patients exposed to hazardous materials. …
609 citations
478 citations
"Molecular Interactions with Mercury..." refers background in this paper
...Current evidence indicates that the organic anion transporter is driven by an organic anion/dicarboxylic acid (dicarboxylate) exchange (reviewed by Pritchard and Miller, 1993, and Dantzler, 1996)....
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...There is evidence that both adipate and glutarate, but not succinate or malonate, can compete with a-ketoglutarate at the site of the organic anion transport system (Ullrich et al., 1987; Pritchard, 1988; Pritchard and Miller, 1993)....
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TL;DR: Urinary enzymes have considerable potential value for the early warning of rejection in transplant patients, screening for renal disease and for the detection of renal damage secondary to hypertension, diabetes and rheumatoid arthritis.
414 citations
"Molecular Interactions with Mercury..." refers background or methods or result in this paper
...As a consequence of this diminished absorptive capacity, there is increased urinary excretion of both water and a number of plasma solutes, such as glucose, amino acids, albumin, and other plasma proteins (Price, 1982; Zalups and Diamond, 1987b; Diamond, 1988; Zalups et al., 1988)....
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...…method that has been used frequently is to measure the urinary excretion of a number of cellular enzymes (Ellis et al., 1973; Planas-Bohne, 1977; Stroo and Hook, 1977; Kirschbaum, 1979; Buchet et al., 1980; Price, 1982; Stonard et al., 1983; Gottelli et al., 1985; Zalups and Diamond, 1987b)....
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...Evidence from several studies shows that the urinary excretion of the brushborder enzymes, alkaline phosphatase and g-GT, increases during the nephropathy induced by mercurycontaining compounds (Price, 1982; Gotelli et al., 1985; Zalups et al., 1988, 1991b)....
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01 Jan 1972
402 citations
"Molecular Interactions with Mercury..." refers background in this paper
...Systemic distributions of organic mercury are more diffuse than inorganic forms, and they affect other target organs, including hematopoietic and neural tissues (Clarkson, 1972; World Health Organization, 1991; Agency for Toxic Substance and Disease Registry, 1999)....
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...Mercuric conjugates of glutathione as transportable forms of mercury at basolateral membrane . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ....
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