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      Heavy Metals and Human Health: Mechanistic Insight into Toxicity and Counter Defense System of Antioxidants

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          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.

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          The role of antioxidants in the chemistry of oxidative stress: A review.

          This Review Article is focused on the action of the reactive oxygenated species in inducing oxidative injury of the lipid membrane components, as well as on the ability of antioxidants (of different structures and sources, and following different mechanisms of action) in fighting against oxidative stress. Oxidative stress is defined as an excessive production of reactive oxygenated species that cannot be counteracted by the action of antioxidants, but also as a perturbation of cell redox balance. Reactive oxygenated/nitrogenated species are represented by superoxide anion radical, hydroxyl, alkoxyl and lipid peroxyl radicals, nitric oxide and peroxynitrite. Oxidative stress determines structure modifications and function modulation in nucleic acids, lipids and proteins. Oxidative degradation of lipids yields malondialdehyde and 4-hydroxynonenal, but also isoprostanes, from unsaturated fatty acids. Protein damage may occur with thiol oxidation, carbonylation, side-chain oxidation, fragmentation, unfolding and misfolding, resulting activity loss. 8-hydroxydeoxyguanosine is an index of DNA damage. The involvement of the reactive oxygenated/nitrogenated species in disease occurrence is described. The unbalance between the oxidant species and the antioxidant defense system may trigger specific factors responsible for oxidative damage in the cell: over-expression of oncogene genes, generation of mutagen compounds, promotion of atherogenic activity, senile plaque occurrence or inflammation. This leads to cancer, neurodegeneration, cardiovascular diseases, diabetes, kidney diseases. The concept of antioxidant is defined, along with a discussion of the existent classification criteria: enzymatic and non-enzymatic, preventative or repair-systems, endogenous and exogenous, primary and secondary, hydrosoluble and liposoluble, natural or synthetic. Primary antioxidants are mainly chain breakers, able to scavenge radical species by hydrogen donation. Secondary antioxidants are singlet oxygen quenchers, peroxide decomposers, metal chelators, oxidative enzyme inhibitors or UV radiation absorbers. The specific mechanism of action of the most important representatives of each antioxidant class (endogenous and exogenous) in preventing or inhibiting particular factors leading to oxidative injury in the cell, is then reviewed. Mutual influences, including synergistic effects are presented and discussed. Prooxidative influences likely to occur, as for instance in the presence of transition metal ions, are also reminded.
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            Peroxynitrite: biochemistry, pathophysiology and development of therapeutics.

            Peroxynitrite--the product of the diffusion-controlled reaction of nitric oxide with superoxide radical--is a short-lived oxidant species that is a potent inducer of cell death. Conditions in which the reaction products of peroxynitrite have been detected and in which pharmacological inhibition of its formation or its decomposition have been shown to be of benefit include vascular diseases, ischaemia-reperfusion injury, circulatory shock, inflammation, pain and neurodegeneration. In this Review, we first discuss the biochemistry and pathophysiology of peroxynitrite and then focus on pharmacological strategies to attenuate the toxic effects of peroxynitrite. These include its catalytic reduction to nitrite and its isomerization to nitrate by metalloporphyrins, which have led to potential candidates for drug development for cardiovascular, inflammatory and neurodegenerative diseases.
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              Free Radicals in Biology and Medicine

              "This latest edition has been comprehensively rewritten and updated (over 80% of the text is new), whilst maintaining the clarity of its predecessor. There is expanded coverage of isoprostanes and related compounds, mechanisms of oxidative damage to DNA and proteins (and the repair of such damage), the free radical theory of ageing and the roles played by reactive species in signal transduction, cell death, human reproduction, and other important biological events. Greater emphasis has also been placed on the methods available to measure reactive species and oxidative damage (and their potential pitfalls), as well as the importance of antioxidants in the human diet." "This book is recommended as a comprehensive introduction to the field for students, clinicians and researchers, and an invaluable companion to all those interested in the role of free radicals in the life and medical sciences."--BOOK JACKET.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                10 December 2015
                December 2015
                : 16
                : 12
                : 29592-29630
                Affiliations
                [1 ]School of Biotechnology, Yeungnam University, Gyeongsan 712-749, Korea
                [2 ]Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India; azammudsser@ 123456gmail.com (M.A.); kehkashansiddiqui7@ 123456gmail.com (K.S.); ali.arifali@ 123456gmail.com (A.A.); haqqmr@ 123456gmail.com (Q.M.R.H.)
                Author notes
                [* ]Correspondence: atasleem@ 123456gmail.com (A.T.J.); inhochoi@ 123456ynu.ac.kr (I.C.); Tel.: +82-53-810-3589 (A.T.J.); +82-53-810-3011 (I.C.)
                [†]

                These authors contributed equally to this work.

                Article
                ijms-16-26183
                10.3390/ijms161226183
                4691126
                26690422
                af8a5602-946a-4ef8-afd5-8ad53a4d093e
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 26 October 2015
                : 03 December 2015
                Categories
                Review

                Molecular biology
                biomolecules,dietary antioxidants,free radicals,heavy metals
                Molecular biology
                biomolecules, dietary antioxidants, free radicals, heavy metals

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