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      Increased Zn/Glutathione Levels and Higher Superoxide Dismutase-1 Activity as Biomarkers of Oxidative Stress in Women with Long-Term Dental Amalgam Fillings: Correlation between Mercury/Aluminium Levels (in Hair) and Antioxidant Systems in Plasma

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          Abstract

          Background

          The induction of oxidative stress by Hg can affect antioxidant enzymes. However, epidemiological studies have failed to establish clear association between dental fillings presence and health problems.

          Objectives

          To determine whether heavy metals (in hair), antioxidant enzymes (SOD-1) and glutathione levels could be affected by the chronic presence of heavy metals in women who had dental amalgam fillings.

          Materials and Methods

          55 hair samples (42 females with amalgam fillings and 13 female control subjects) were obtained. All subjects (mean age 44 years) who had dental amalgam filling for more than 10 years (average 15 years). Certain metals were quantified by ICP-MS (Mass Spectrophotometry) in hair (μg/g: Al, Hg, Ba, Ag, Sb, As, Be, Bi, Cd, Pb, Pt, Tl, Th, U, Ni, Sn, Ti) and SOD-1 and Glutathione (reduced form) levels in plasma. Data were compared with controls without amalgams, and analyzed to identify any significant relation between metals and the total number of amalgam fillings, comparing those with four or less (n = 27) with those with more than four (n = 15). As no significant differences were detected, the two groups were pooled (Amlgam; n = 42).

          Findings

          Hg, Ag, Al and Ba were higher in the amalgam group but without significant differences for most of the heavy metals analyzed. Increased SOD-1 activity and glutathione levels (reduced form) were observed in the amalgam group. Aluminum (Al) correlated with glutathione levels while Hg levels correlated with SOD-1. The observed Al/glutathione and Hg/SOD-1 correlation could be adaptive responses against the chronic presence of mercury.

          Conclusions

          Hg, Ag, Al and Ba levels increased in women who had dental amalgam fillings for long periods. Al correlated with glutathione, and Hg with SOD-1. SOD-1 may be a possible biomarker for assessing chronic Hg toxicity.

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          Most cited references33

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          Human Exposure and Health Effects of Inorganic and Elemental Mercury

          Mercury is a toxic and non-essential metal in the human body. Mercury is ubiquitously distributed in the environment, present in natural products, and exists extensively in items encountered in daily life. There are three forms of mercury, i.e., elemental (or metallic) mercury, inorganic mercury compounds, and organic mercury compounds. This review examines the toxicity of elemental mercury and inorganic mercury compounds. Inorganic mercury compounds are water soluble with a bioavailability of 7% to 15% after ingestion; they are also irritants and cause gastrointestinal symptoms. Upon entering the body, inorganic mercury compounds are accumulated mainly in the kidneys and produce kidney damage. In contrast, human exposure to elemental mercury is mainly by inhalation, followed by rapid absorption and distribution in all major organs. Elemental mercury from ingestion is poorly absorbed with a bioavailability of less than 0.01%. The primary target organs of elemental mercury are the brain and kidney. Elemental mercury is lipid soluble and can cross the blood-brain barrier, while inorganic mercury compounds are not lipid soluble, rendering them unable to cross the blood-brain barrier. Elemental mercury may also enter the brain from the nasal cavity through the olfactory pathway. The blood mercury is a useful biomarker after short-term and high-level exposure, whereas the urine mercury is the ideal biomarker for long-term exposure to both elemental and inorganic mercury, and also as a good indicator of body burden. This review discusses the common sources of mercury exposure, skin lightening products containing mercury and mercury release from dental amalgam filling, two issues that happen in daily life, bear significant public health importance, and yet undergo extensive debate on their safety.
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            Cadmium induces reactive oxygen species generation and lipid peroxidation in cortical neurons in culture.

            Cadmium is a toxic agent that it is also an environmental contaminant. Cadmium exposure may be implicated in some humans disorders related to hyperactivity and increased aggressiveness. This study presents data indicating that cadmium induces cellular death in cortical neurons in culture. This death could be mediated by an apoptotic and a necrotic mechanism. The apoptotic death may be mediated by oxidative stress with reactive oxygen species (ROS) formation which could be induced by mitochondrial membrane dysfunction since this cation produces: (a) depletion of mitochondrial membrane potential and (b) diminution of ATP levels with ATP release. Necrotic death could be mediated by lipid peroxidation induced by cadmium through an indirect mechanism (ROS formation). On the other hand, 40% of the cells survive cadmium action. This survival seems to be mediated by the ability of these cells to activate antioxidant defense systems, since cadmium reduced the intracellular glutathione levels and induced catalase and SOD activation in these cells.
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              Oxidative stress in MeHg-induced neurotoxicity.

              Methylmercury (MeHg) is an environmental toxicant that leads to long-lasting neurological and developmental deficits in animals and humans. Although the molecular mechanisms mediating MeHg-induced neurotoxicity are not completely understood, several lines of evidence indicate that oxidative stress represents a critical event related to the neurotoxic effects elicited by this toxicant. The objective of this review is to summarize and discuss data from experimental and epidemiological studies that have been important in clarifying the molecular events which mediate MeHg-induced oxidative damage and, consequently, toxicity. Although unanswered questions remain, the electrophilic properties of MeHg and its ability to oxidize thiols have been reported to play decisive roles to the oxidative consequences observed after MeHg exposure. However, a close examination of the relationship between low levels of MeHg necessary to induce oxidative stress and the high amounts of sulfhydryl-containing antioxidants in mammalian cells (e.g., glutathione) have led to the hypothesis that nucleophilic groups with extremely high affinities for MeHg (e.g., selenols) might represent primary targets in MeHg-induced oxidative stress. Indeed, the inhibition of antioxidant selenoproteins during MeHg poisoning in experimental animals has corroborated this hypothesis. The levels of different reactive species (superoxide anion, hydrogen peroxide and nitric oxide) have been reported to be increased in MeHg-exposed systems, and the mechanisms concerning these increments seem to involve a complex sequence of cascading molecular events, such as mitochondrial dysfunction, excitotoxicity, intracellular calcium dyshomeostasis and decreased antioxidant capacity. This review also discusses potential therapeutic strategies to counteract MeHg-induced toxicity and oxidative stress, emphasizing the use of organic selenocompounds, which generally present higher affinity for MeHg when compared to the classically studied agents. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                15 June 2015
                2015
                : 10
                : 6
                : e0126339
                Affiliations
                [1 ]Centro CIROM, Centro de Implantología y Rehabilitación Oral Multidisciplinaria, Murcia, Spain
                [2 ]Facultad de Medicina, Universidad de Murcia, UMU, Unidad Docente de Ortodoncia, Murcia, Spain
                [3 ]Department of Orthodontics, Dental School, Kyungpook Nacional University, Daegu, Korea
                [4 ]IUIN, Instituto de Investigación Neuroquímica, Universidad Complutense de Madrid, (U.C.M), Madrid, Spain
                University of Sassari, ITALY
                Author notes

                Competing Interests: The authors declare that there are no conflicts of interest. All authors do not have competing interests and financial disclosures that declare from CIROM or other affiliations. There is no employment, consultancy, patents, or products in development that could interfere with the publication of this manuscript in PLOS ONE. The authors confirm that this does not affect PLOS ONE policies on sharing data and materials, as detailed online in our guide for authors. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: MEC JMP LAB HMK JJM. Performed the experiments: MEC JMP JJM. Analyzed the data: JJM HMK LAB. Contributed reagents/materials/analysis tools: JJM LAB MEC. Wrote the paper: JJM MEC. Samples colection: MEC HMK JMP.

                Article
                PONE-D-14-42314
                10.1371/journal.pone.0126339
                4468144
                26076368
                1318a84b-7610-4231-b22d-b6f16b0f1de3
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 1 October 2014
                : 1 April 2015
                Page count
                Figures: 2, Tables: 1, Pages: 11
                Funding
                This study has been supported by own findings from Maria Eugenia Cabaña (CIROM Clinic (Murcia, Spain; personnal money). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                All relevant data are included within the paper.

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