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Title: Oxidative stress in MeHg-induced neurotoxicity

Abstract

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 bemore » 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.« less

Authors:
 [1];  [2];  [3];  [4]
  1. Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Florianopolis, SC (Brazil)
  2. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (United States)
  3. (United States)
  4. Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil)
Publication Date:
OSTI Identifier:
22212543
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 256; Journal Issue: 3; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIONS; ANTIOXIDANTS; BIOLOGICAL STRESS; CALCIUM; GLUTATHIONE; HYDROGEN PEROXIDE; INHIBITION; METHYLMERCURY; MITOCHONDRIA; NITRIC OXIDE; OXIDATION; REVIEWS; THIOLS; TOXICITY

Citation Formats

Farina, Marcelo, E-mail: farina@ccb.ufsc.br, Aschner, Michael, Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, and Rocha, Joao B.T., E-mail: jbtrocha@yahoo.com.br. Oxidative stress in MeHg-induced neurotoxicity. United States: N. p., 2011. Web. doi:10.1016/J.TAAP.2011.05.001.
Farina, Marcelo, E-mail: farina@ccb.ufsc.br, Aschner, Michael, Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, & Rocha, Joao B.T., E-mail: jbtrocha@yahoo.com.br. Oxidative stress in MeHg-induced neurotoxicity. United States. doi:10.1016/J.TAAP.2011.05.001.
Farina, Marcelo, E-mail: farina@ccb.ufsc.br, Aschner, Michael, Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, and Rocha, Joao B.T., E-mail: jbtrocha@yahoo.com.br. Tue . "Oxidative stress in MeHg-induced neurotoxicity". United States. doi:10.1016/J.TAAP.2011.05.001.
@article{osti_22212543,
title = {Oxidative stress in MeHg-induced neurotoxicity},
author = {Farina, Marcelo, E-mail: farina@ccb.ufsc.br and Aschner, Michael and Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN and Rocha, Joao B.T., E-mail: jbtrocha@yahoo.com.br},
abstractNote = {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.},
doi = {10.1016/J.TAAP.2011.05.001},
journal = {Toxicology and Applied Pharmacology},
number = 3,
volume = 256,
place = {United States},
year = {Tue Nov 15 00:00:00 EST 2011},
month = {Tue Nov 15 00:00:00 EST 2011}
}