Methylmercury neurotoxicity and antioxidant defenses. Indian J Med Res

Lab. Neuroquímica Molecular e Celular, Dep. Fisiologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil.
The Indian Journal of Medical Research (Impact Factor: 1.4). 11/2008; 128(4):373-82.
Source: PubMed


Neurotoxicity induced by methylmercury (MeHg) increases the formation of reactive radicals and accelerates free radical reactions. This review summarizes recent findings in the MeHg-induced formation of free radicals and the role of oxidative stress in its neurotoxicity. Oxidative stress on CNS can produce damage by several interacting mechanisms, including mitochondrial damage with increase in intracellular free Ca(2+), activation and inhibition of enzymes, release of excitatory amino acids, metallothioneins expression, and microtubule disassembly. The nature of antioxidants is discussed and it is suggested that antioxidant enzymes and others antioxidants molecules may protect the central nervous system against neurotoxicity caused by MeHg.

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Available from: Maria Elena Crespo-López
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    • "All of these mechanisms relate at least in part to Hg's high affinity for the sulfhydryl or thiol group. Oxidative stress is perhaps the best studied biochemical response to Hg intoxication, although the specific mechanism by which methyl mercury (MeHg) causes oxidative stress is poorly understood (Nascimento et al. 2008). Mercury induces the formation of reactive oxygen species (ROS) but also directly binds glutathione (GSH) thereby depleting this major antioxidant defense system (Ercal et al. 2001). "
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    ABSTRACT: Historical discharges of Hg into the South River near the town of Waynesboro, VA, USA, have resulted in persistently elevated Hg concentrations in sediment, surface water, ground water, soil, and wildlife downstream of the discharge site. In the present study, we examined mercury (Hg) levels in in little brown bats (Myotis lucifugus) from this location and assessed the utility of a non-destructively collected tissue sample (wing punch) for determining mitochondrial DNA (mtDNA) damage in Hg exposed bats. Bats captured 1 and 3 km from the South River, exhibited significantly higher levels of total Hg (THg) in blood and fur than those from the reference location. We compared levels of mtDNA damage using real-time quantitative PCR (qPCR) analysis of two distinct regions of mtDNA. Genotoxicity is among the many known toxic effects of Hg, resulting from direct interactions with DNA or from oxidative damage. Because it lacks many of the protective protein structures and repair mechanisms associated with nuclear DNA, mtDNA is more sensitive to the effects of genotoxic chemicals and therefore may be a useful biomarker in chronically exposed organisms. Significantly higher levels of damage were observed in both regions of mtDNA in bats captured 3 km from the river than in controls. However, levels of mtDNA damage exhibited weak correlations with fur and blood THg levels, suggesting that other factors may play a role in the site-specific differences.
    Full-text · Article · Jul 2014 · Ecotoxicology
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    • "Alterations in their levels may contribute to MeHg neurotoxicity which could have further implications should the offspring be exposed to a subsequent neurotoxic insult. One of the major mechanisms of MeHg toxicity is the disruption of antioxidant defences (Nascimento et al. 2008; Farina et al. 2011b). MeHg has been shown to impair the glutathione antioxidant system by binding readily to glutathione leading to glutathione depletion (Farina et al. 2011b; Kaur et al. 2011). "
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    ABSTRACT: Methylmercury (MeHg) is a metal toxin found commonly in the environment. Studies have shown severe neurotoxic effects of MeHg poisoning especially during pregnancy where it crosses the foetoplacental and the blood brain barrier of the foetus leading to neurodevelopmental deficits in the offspring. These deficits may predispose offspring to neurodegenerative diseases later in life. In this study we investigated the effects of prenatal methylmercury exposure (2.5 mg/L in drinking water from GND 1-GND 21) on the trace element status in the brain of adolescent offspring (PND 28). Total antioxidant capacity (TAC) was measured in their blood plasma. In a separate group of animals that was also exposed prenatally to MeHg, 6-hydroydopamine (6-OHDA) was administered at PND 60 as a model of neuronal insult. Trace element and TAC levels were compared before and after 6-OHDA exposure. Prenatal MeHg treatment alone resulted in significantly higher concentrations of zinc, copper, manganese and selenium in the brain of offspring at PND 28 (p < 0.05), when compared to controls. In contrast, brain iron levels in MeHg-exposed adolescent offspring were significantly lower than their controls (p < 0.05). Following 6-OHDA exposure, the levels of iron, zinc, copper and manganese were increased compared to sham-lesioned offspring (p < 0.05). Prenatal MeHg exposure further increased these trace element levels thereby promoting toxicity (p < 0.05). Total antioxidant capacity was not significantly different in MeHg and control groups prior to lesion. However, following 6-OHDA administration, MeHg-exposed animals had a significantly lower TAC than that of controls (p < 0.05). Brain TAC levels were higher in adult male rats than in female rats during adolescence however male rats that had been exposed to MeHg in utero failed to show this increase at PND 74. Prenatal MeHg exposure results in trace element dyshomeostasis in the brain of offspring and reduces total antioxidant capacity. This may reflect a mechanism by which methylmercury exerts its neurotoxicity and/or predispose offspring to further neurological insults during adulthood.
    Full-text · Article · Dec 2013 · Metabolic Brain Disease
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    • "This toxicant inhibits cysteine uptake in astrocytes and the activity of glutathione peroxidase, thereby depleting intracellular glutathione levels (Aschner et al., 2007; Franco et al., 2009; Shanker et al., 2001, 2005). MeHg also inhibits glutamate uptake in glial cells, producing a glutamatergic accumulation in the synaptic cleft and, ultimately, resulting in further increases in ROS formation and excitotoxicity (Aschner et al., 2007; Nascimento et al., 2008). "
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    ABSTRACT: Adult zebrafish were treated acutely with methylmercury (1.0 or 5.0 μg g(-1), i.p.) and, 24h after treatment, were tested in two behavioral models of anxiety, the novel tank and the light/dark preference tests. At the smaller dose, methylmercury produced a marked anxiogenic profile in both tests, while the greater dose produced hyperlocomotion in the novel tank test. These effects were accompanied by a decrease in extracellular levels of serotonin, and an increase in extracellular levels of tryptamine-4,5-dione, a partially oxidized metabolite of serotonin. A marked increase in the formation of malondialdehyde, a marker of oxidative stress, accompanied these parameters. It is suggested that methylmercury-induced oxidative stress produced mitochondrial dysfunction and originated tryptamine-4,5-dione, which could have further inhibited tryptophan hydroxylase. These results underscore the importance of assessing acute, low-level neurobehavioral effects of methylmercury.
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