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Biomedical Implications of Heavy Metals Induced Imbalances in Redox Systems

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Biomedical Implications of Heavy Metals Induced Imbalances in Redox Systems Hindawi Publishing Corporation BioMed Research International Volume 2014, Article ID 640754, 26 pages http://dx.doi.org/10.1155/2014/640754 Review Article Biomedical Implications of Heavy Metals Induced Imbalances in Redox Systems Bechan Sharma,1 Shweta Singh,2 and Nikhat J. Siddiqi3 1 Department of Biochemistry, University of Allahabad, Allahabad 211002, India 2 Department of Genetics, SGPGIMS, Lucknow 226014, India 3 Department of Biochemistry, King Saud University, Riyadh 11451, Saudi Arabia Correspondence should be addressed to Bechan Sharma; [email protected] Received 28 February 2014; Revised 28 May 2014; Accepted 10 July 2014; Published 12 August 2014 Academic Editor: Hartmut Jaeschke Copyright © 2014 Bechan Sharma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Several workers have extensively worked out the metal induced toxicity and have reported the toxic and carcinogenic effects of metals in human and animals. It is well known that these metals play a crucial role in facilitating normal biological functions of cells as well. One of the major mechanisms associated with heavy metal toxicity has been attributed to generation of reactive oxygen and nitrogen species, which develops imbalance between the prooxidant elements and the antioxidants (reducing elements) in the body. In this process, a shift to the former is termed as oxidative stress. The oxidative stress mediated toxicity of heavy metals involves damage primarily to liver (hepatotoxicity), central nervous system (neurotoxicity), DNA (genotoxicity), and kidney (nephrotoxicity) in animals and humans. Heavy metals are reported to impact signaling cascade and associated factors leading to apoptosis. The present review illustrates an account of the current knowledge about the effects of heavy metals (mainly arsenic, lead, mercury, and cadmium) induced oxidative stress as well as the possible remedies of metal(s) toxicity through natural/synthetic antioxidants, which may render their effects by reducing the concentration of toxic metal(s). This paper primarily concerns the clinicopathological and biomedical implications of heavy metals induced oxidative stress and their toxicity management in mammals. 1. Introduction Heavy metals are natural components of the earth’s crust. These elements are the oldest toxins known to humans, Many different definitions for heavy metals have been pro- having been used for thousands of years. Potential sources posed, some based on density, some on atomic number or of heavy metals exposure include natural sources (e.g., atomic weight, and some on chemical properties or toxicity. groundwater, metal ores), industrial processes, commercial The group of heavy metals can include elements lighter products, folk remedies, and contaminated food and herbal than carbon and can exclude some of the heaviest metals. products. Virtually all heavy metals are toxic in sufficient One of such definitions entails that heavy metals are those quantities. Because of their concentrations in the environ- inorganic elements which have five times the specific gravity ment lead, mercury, and arsenic are of particular interest. of water. Among the heavy metals having serious health Entering our bodies by way of food, drinking water, and implications are arsenic, lead, cadmium, and mercury [1]. air, metals produce toxicity by forming complexes with Theaccumulationoftheseelementscancauseseveredamage cellular compounds containing sulfur, oxygen, or nitrogen. to mucus tissues and intestinal tract and skeletal, central The complexes inactivate enzyme systems or modify critical nervous, and reproductive systems. In addition to the toxic protein structures leading to cellular dysfunction and death. and carcinogenic effects of some metals in humans and The most commonly affected organ systems include animals, they also play pivotal role in mediating a balanced central nervous, gastrointestinal (GI), cardiovascular, biological functioning of cells. hematopoietic, renal, and peripheral nervous systems. The 2 BioMed Research International Table 1: Brief description of some reactive oxygen species (ROS). Reactive oxygen species (ROS) Oxidant Description ROS contain nonradicals ...and radicals One-electron reduction state of O2,formed H O H in many autoxidation reactions and by the Molecules O O − electron transport chain. Rather unreactive Hydroxyl ∙O2 , H ∙ but can release Fe2+ from iron-sulfur Hydrogen radical (OH ) O O H superoxide proteins and ferritin. Undergoes peroxide (H2O2) anion Hydroperoxyl dismutation to form H O spontaneously or − − ∙ 2 2 radical (HO 2 ) by enzymatic catalysis and is a precursor for Ions: O Cl O O metal-catalyzed ∙OH formation. Hypochlorite Superoxide − ∙− Two-electron reduction state, formed by ion (OCl ) anion (O 2 ) ∙ − H2O2, hydrogen dismutation of O2 or by direct reduction peroxide of O2. Lipid soluble and thus able to diffuse across membranes. Figure 1: Reactive oxygen species (ROS) existing in radicals and Three-electron reduction state, formed by nonradicals forms. ∙OH, hydroxyl Fenton reaction and decomposition of radical peroxynitrite. Extremely reactive and will attack most cellular components. natureandseverityoftoxicityvarywiththeheavymetal ROOH, organic Formed by radical reactions with cellular involved, its exposure level, chemical and valence states hydroperoxide components such as lipids and nucleobases. (inorganic versus organic), mode of exposure (acute versus Oxygen centred organic radicals. Lipid RO∙,alkoxy, chronic), and the age of the individual. Children with their forms participate in reactions. Produced in and ROO∙, developing nervous systems are particularly vulnerable to the presence of oxygen by radical addition peroxy radicals heavy metal intoxication (especially lead). to double bonds or hydrogen abstraction. The heavy metals induced toxicity has been extensively Formed from H2O2 by myeloperoxidase. studied and reported by various workers. They have demon- HOCl, Lipid soluble and highly reactive. Will strated that the exposure of an animal to excess concen- hypochlorous readily oxidize protein constituents, trations of these elements may augment production of free acid including thiol groups, amino groups, and radicals which may cause oxidative stress [2–5]. In fact methionine. − generation of oxidative stress has been considered as one Formed in a rapid reaction between ∙O2 of the major mechanisms behind heavy metal toxicity. The and NO∙. Lipid soluble and similar in − heavy metals have potential towards production of the highly ONOO , reactivity to hypochlorous acid. Protonation reactive chemical entities such as free radicals having the peroxynitrite forms peroxynitrous acid, which can ability to cause lipid peroxidation, DNA damage, oxidation undergo homolytic cleavage to form of sulfhydryl groups of proteins, depletion of protein, and hydroxyl radical and nitrogen dioxide. several other effects [3]. The heavy metals have been found to generate reactive oxygen species (ROS), which in turn results in their toxic effects in the form of hepatotoxicity and pentavalent arsenate (As (V)), and elemental. Arsenite is ten neurotoxicity as well as nephrotoxicity in both animals and times more toxic than arsenate; elemental arsenic is non- humans [2, 4].Someofthereactiveoxygenspeciesareshown toxic. Arsenic also exists in three chemical forms: organic, in Figure 1. Their few characteristic properties and impact on inorganic, and arsine gas, with organic arsenic having little cellular systems are summarized in Table 1. toxicity whereas inorganic arsenic and arsine gas are toxic. Thisreviewsummarizesanupdatedaccountofavailable It is widely distributed in nature and utilizes its three most information on heavy metals induced imbalance in the redox common oxidation numbers (+5, +3, and –3) to form chemi- systems in the body and their clinical and pathophysiological cal complexes in body. A summary of environmental sources implications as well as use of certain natural and synthetic ofarsenicaswellastheirpotentialhealtheffectsismen- products to mitigate their toxicity. It illustrates toxic effects of tioned in the National Research Council report on arsenic only four key heavy metals such as arsenic, lead, cadmium, in drinking water. Most major US drinking water supplies and mercury, which are ubiquitous in air and water pollutants contain levels lower than 5 g/L. It has been estimated that that continue to threaten the quality of public health around about 350,000 thousand people might drink water containing the world. These elements are associated with many adverse more than 50 g/L [7]. Exposure to arsenic primarily occurs health effects generated through oxidative damage and dis- by ingestion, but inhalation and absorption through the skin ease processes [5]. are possible. Arsenic occurs naturally in seafood as nontoxic organic compounds, such as arsenobetaine, which can cause 2. Arsenic elevated urine arsenic levels. The lethal dose of inorganic arsenic has been estimated to be 0.6 mg/kg. Arsenic is particularly difficult to characterize as a single About 80–90% of a single dose of arsenite As (III) element because its chemistry is really complex. Arsenic or arsenate As (V) has been shown to be absorbed from occurs in three oxidation states: trivalent arsenite (As (III)), the gastrointestinal (GI) tract of humans and experimental BioMed Research
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