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Methylmercury - MeHg

Methylmercury Epigenetics
Published: 2019
SYNOPSIS

In the brain, MeHg seems to induce epigenetic modifications, which disrupt typical neuronal differentiation. These results correlate well with known effects on this developmental process

CITATION

Culbreth, M and Aschner, M.; Toxics 2019, 7, 56; doi:10.3390/toxics7040056

SUMMARY

Methylmercury (MeHg) has conventionally been investigated for effects on nervous system development. As such, epigenetic modifications have become an attractive mechanistic target, and research on MeHg and epigenetics has rapidly expanded in the past decade. Although, these inquiries are a recent advance in the field, much has been learned in regards to MeHg-induced epigenetic modifications, particularly in the brain.In vitro and in vivo controlled exposure studies illustrate that MeHg effects microRNA (miRNA) expression, histone modifications, and DNA methylation both globally and at individual genes. Moreover, some effects are transgenerationally inherited, as organisms not directly exposed to MeHg exhibited biological and behavioral alterations. miRNA expression generally appears to be down regulated consequent to exposure. Further, global histone acetylation also seems to be reduced, persist at distinct gene promoters, and is contemporaneous with enhanced histone methylation. Moreover, global DNA methylation appears to decrease in brain-derived tissues, but not in the liver; however, selected individual genes in the brain are hypermethylated. Human epidemiological studies have also identified hypo- or hypermethylated individual genes, which correlated with MeHg exposure in distinct populations. Intriguingly, several observed epigenetic modifications can be correlated with known mechanisms of MeHg toxicity.Despite this knowledge, however, the functional consequences of these modifications are not entirely evident. Additional research will be necessary to fully comprehend MeHg-induced epigenetic modifications and the impact on the toxic response.

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Rethinking mercury: the role of selenium in the pathophysiology of mercury toxicity
Published: 2017
SYNOPSIS

Mercury in the body produces a selenium deficiency state that increases toxicity.

CITATION

Spiller HA. Rethinking mercury: the role of selenium in the pathophysiology of mercury toxicity. Clinical Toxicology. 2018;56(5):313-326.

SUMMARY

This study makes the case that mercury’s multifaceted interactions with selenium are a central feature of mercury toxicity. The authors argue that “the previously suggested ‘protective effect’ of selenium against mercury toxicity may in fact be backwards”—because of mercury’s affinity for selenium, mercury can actually produce a selenium deficiency state that promotes oxidative stress and inhibits the body’s regenerative mechanisms. Depending on the form of mercury and other factors, selenium supplementation may have some benefits for restoring adequate selenium status and mitigating the toxicity of mercury, but it does not appear to promote increased elimination of mercury.

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Toxicity of organic and inorganic mercury species in differentiated human neurons and human astrocytes
Published: 2015
SYNOPSIS

Thimerosal and methylmercury cause cell death in human neurons.

CITATION

Lohren H, Blagojevic L, Fitkau R, et al. Journal of Trace Elements in Medicine and Biology. 2015;32:200–208.

SUMMARY

Thimerosal and methylmercury caused cell death in differentiated human neurons and astrocytes. Differentiated neurons showed a massive uptake of ethylmercury (degradation product of thimerosal). This affirms the type of neural damage seen in patients with autism.

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Low-dose mercury exposure in early life: Relevance of thimerosal to fetuses, newborns and infants
Published: 2013
SYNOPSIS

There is a connection between infant and prenatal thimerosal exposure and neurological disorders.

CITATION

Dórea JG. Current Medicinal Chemistry. 2013;20:4060-4069.

SUMMARY

This review article highlights the scientifically affirmed connection between infant and prenatal thimerosal exposure and neurological disorders, including tic disorder, which has been shown to be much more prevalent in children with autism. The author also delineates the use of thimerosal in vaccines in developing countries at a greater exposure level than developed countries such as the U.S.

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Maternal Thimerosal Exposure Results in Aberrant Cerebellar Oxidative Stress, Thyroid Hormone Metabolism, and Motor Behavior in Rat Pups; Sex- and Strain-Dependent Effects
Published: 2011
SYNOPSIS

Harvard researchers find vaccine mercury impacts neurodevelopment in rats.

CITATION

Z. L. Sulkowski & T. Chen & S. Midha & A. M. Zavacki & Elizabeth M. Sajdel-Sulkowska. Cerebellum, (2012) 11:575–586.

SUMMARY

“Our data indicate that maternal TM exposure results in a delayed auditory maturation and impaired motor learning in rat pups. Factors that may contribute to these abnormalities include increased cerebellar oxidative stress and decreased D2 activity resulting local intracerebellar T3 deficiency and altered TH-dependent gene expression. Indeed, provided here is the first evidence of altered TH-dependent gene expression following TM exposure. Our data thus demonstrate a negative neurodevelopmental impact of perinatal TM exposure, which appears to be both strain- and sex-dependent. Although, additional studies are needed, data derived from TM exposure in rats may provide clues relevant to understanding neurodevelopmental consequences of TM exposure in humans.”

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Comparison of Blood and Brain Mercury Levels in Infant Monkeys Exposed to Methylmercury or Vaccines Containing Thimerosal
Published: 2005
SYNOPSIS

The mercury used as a vaccine preservative is far more neurotoxic than the mercury found in fish.

CITATION

Thomas M. Burbacher, Danny D. Shen, Noelle Liberato, Kimberly S. Grant, Elsa Cernichiari, and Thomas Clarkson. Environmental Health Perspectives, Volume 113, Number 8, August 2005.

SUMMARY

The mercury used in vaccines (and still in the flu vaccine given to pregnant women) is far more toxic than the mercury found in fish, because it stays in the brain at much higher levels. “Data from the present study support the prediction that, although little accumulation of Hg in the blood occurs over time with repeated vaccinations, accumulation of Hg in the brain of infants will occur. Thus, conclusion regarding the safety of thimerosal drawn from blood Hg clearance data in human infants receiving vaccines may not be valid, given the significantly slower half-life of Hg in the brain as observed in the infant macaques. There was a much higher proportion of inorganic Hg in the brain of thimerosal monkeys than in the brains of MeHg monkeys (up to 71% vs. 10%). Absolute inorganic Hg concentrations in the brains of the thimerosal-exposed monkeys were approximately twice that of the MeHg monkeys.”

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Public health and economic consequences of methyl mercury toxicity to the developing brain
Published: 2005
SYNOPSIS

In utero exposure to methylmercury from power plants and seafood is associated with lifelong loss of intelligence and billions of dollars in lost productivity.

CITATION

Trasande L, Landrigan PJ, Schechter C. Public health and economic consequences of methyl mercury toxicity to the developing brain. Environmental Health Perspectives. 2005;113(5):590-596.

SUMMARY

This study shows that the IQ losses associated with methylmercury toxicity cost the U.S. economy billions of dollars in lost productivity each year. Hundreds of thousands of American children in any given year have cord blood levels of methylmercury associated with lowered intelligence, traceable to in utero exposure to power plant emissions or to maternal seafood consumption. The loss of intelligence that results “causes diminished economic productivity that persists over the entire lifetime of these children”—amounting to about $8.7 billion annually.

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Thimerosal Neurotoxicity is Associated with Glutathione Depletion: Protection with Glutathione Precursors
Published: 2005
SYNOPSIS

Vaccine mercury depletes a vital antioxidant, glutathione.

CITATION

S.J. James, William Slikker, Stepan Melnyk, Elizabeth New,
Marta Pogribna, Stefanie Jernigan. NeuroToxicology, 26 (2005) 1–8.

SUMMARY

“Thimerosal is an antiseptic containing 49.5% ethyl mercury that has been used for years as a preservative in many infant vaccines and in flu vaccines. Environmental methyl mercury has been shown to be highly neurotoxic, especially to the developing brain. Because mercury has a high affinity for thiol (sulfhydryl (-SH)) groups, the thiol-containing antioxidant, glutathione (GSH), provides the major intracellular defense against mercury-induced neurotoxicity. Cultured neuroblastoma cells were found to have lower levels of GSH and increased sensitivity to thimerosal toxicity compared to glioblastoma cells that have higher basal levels of intracellular GSH. Thimerosal-induced cytotoxicity was associated with depletion of intracellular GSH in both cell lines. Although Thimerosal has been recently removed from most children’s vaccines, it is still present in flu vaccines given to pregnant women, the elderly, and to children in developing countries.”

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