Mercury

Antioxidant / Autism Biomarkers / Detoxification / Glutathione / Mercury / Mitochondria / Oxidative Stress / Sulfhydryl Groups / Thimerosal / Toxicants

Cellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism

Excerpt:
“Exposure to oxidative stress via the sulfhydryl reagent thimerosal resulted in a greater decrease in the GSH/GSSG ratio and increase in free radical generation in autism compared to control cells. Acute exposure to physiological levels of nitric oxide decreased mitochondrial membrane potential to a greater extent in the autism LCLs, although GSH/GSSG and ATP concentrations were similarly decreased in both cell lines. These results suggest that the autism LCLs exhibit a reduced glutathione reserve capacity in both cytosol and mitochondria that may compromise antioxidant defense and detoxification capacity under prooxidant conditions.”

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  • March 23, 2009
Hepatitis B Vaccine / Mercury / Parental reports / Thimerosal / Toxicants / Unvaccinated

Hepatitis B triple series vaccine and developmental disability in US children aged 1–9 years

Excerpt:
“This study found statistically significant evidence to suggest that boys in United States who were vaccinated with the triple series Hepatitis B vaccine, during the time period in which vaccines were manufactured with thimerosal, were more susceptible to developmental disability than were unvaccinated boys.”

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  • September 5, 2008
Males / Mercury / Thimerosal / Toxicants

Gender-selective toxicity of thimerosal.

Abstract
A recent report shows a correlation of the historical use of thimerosal in therapeutic immunizations with the subsequent development of autism; however, this association remains controversial. Autism occurs approximately four times more frequently in males compared to females; thus, studies of thimerosal toxicity should take into consideration gender-selective effects. The present study was originally undertaken to determine the maximum tolerated dose (MTD) of thimersosal in male and female CD1 mice. However, during the limited MTD studies, it became apparent that thimerosal has a differential MTD that depends on whether the mouse is male or female. At doses of 38.4-76.8mg/kg using 10% DMSO as diluent, seven of seven male mice compared to zero of seven female mice tested succumbed to thimerosal. Although the thimerosal levels used were very high, as we were originally only trying to determine MTD, it was completely unexpected to observe a difference of the MTD between male and female mice. Thus, our studies, although not directly addressing the controversy surrounding thimerosal and autism, and still preliminary due to small numbers of mice examined, provide, nevertheless, the first report of gender-selective toxicity of thimerosal and indicate that any future studies of thimerosal toxicity should take into consideration gender-specific differences.

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  • September 3, 2008
Mercury / Porphyrin / Thimerosal / Toxicants

An investigation of porphyrinuria in Australian children with autism

Abstract
Two recent studies, from France (Nataf et al., 2006) and the United States (Geier & Geier, 2007), identified atypical urinary porphyrin profiles in children with an autism spectrum disorder (ASD). These profiles serve as an indirect measure of environmental toxicity generally, and mercury (Hg) toxicity specifically, with the latter being a variable proposed as a causal mechanism of ASD (Bernard et al., 2001; Mutter et al., 2005). To examine whether this phenomenon occurred in a sample of Australian children with ASD, an analysis of urinary porphyrin profiles was conducted. A consistent trend in abnormal porphyrin levels was evidenced when data was compared with those previously reported in the literature. The results are suggestive of environmental toxic exposure impairing heme synthesis. Three independent studies from three continents have now demonstrated that porphyrinuria is concomitant with ASD, and that Hg may be a likely xenobiotic to produce porphyrin profiles of this nature.

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  • August 21, 2008
Antioxidant / Mercury / Oxidative Stress / Thimerosal / Toxicants

Oxidative Stress in Autism: Elevated Cerebellar 3-nitrotyrosine Levels

Shows a potential link between mercury and the autopsied brains of young people with autism. A marker for oxidative stress was 68.9% higher in autistic brain issue than controls (a statistically significant result), while mercury levels were 68.2% higher.

Excerpt:
“The preliminary data suggest a need for more extensive studies of oxidative stress, its relationship to the environmental factors and its possible attenuation by antioxidants in autism.”

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  • June 30, 2008
Glutathione / Mercury / Thimerosal / Thioredoxin / Toxicants

Inhibition of the human thioredoxin system. A molecular mechanism of mercury toxicity.

Abstract

Mercury toxicity mediated by different forms of mercury is a major health problem; however, the molecular mechanisms underlying toxicity remain elusive. We analyzed the effects of mercuric chloride (HgCl(2)) and monomethylmercury (MeHg) on the proteins of the mammalian thioredoxin system, thioredoxin reductase (TrxR) and thioredoxin (Trx), and of the glutaredoxin system, glutathione reductase (GR) and glutaredoxin (Grx). HgCl(2) and MeHg inhibited recombinant rat TrxR with IC(50) values of 7.2 and 19.7 nm, respectively. Fully reduced human Trx1 bound mercury and lost all five free thiols and activity after incubation with HgCl(2) or MeHg, but only HgCl(2) generated dimers. Mass spectra analysis demonstrated binding of 2.5 mol of Hg(2+) and 5 mol of MeHg(+)/mol of Trx1 with the very strong Hg(2+) complexes involving active site and structural disulfides. Inhibition of both TrxR and Trx activity was observed in HeLa and HEK 293 cells treated with HgCl(2) or MeHg. GR was inhibited by HgCl(2) and MeHg in vitro, but no decrease in GR activity was detected in cell extracts treated with mercurials. Human Grx1 showed similar reactivity as Trx1 with both mercurial compounds, with the loss of all free thiols and Grx dimerization in the presence of HgCl(2), but no inhibition of Grx activity was observed in lysates of HeLa cells exposed to mercury. Overall, mercury inhibition was selective toward the thioredoxin system. In particular, the remarkable potency of the mercury compounds to bind to the selenol-thiol in the active site of TrxR should be a major molecular mechanism of mercury toxicity.

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  • March 4, 2008
Mercury / Toxicants

Proximity to point sources of environmental mercury release as a predictor of autism prevalence

Abstract

This study should be viewed as hypothesis-generating – a first step in examining the potential role of environmental mercury and childhood developmental disorders. Nothing is known about specific exposure routes, dosage, timing, and individual susceptibility. We suspect that persistent low-dose exposures to various environmental toxicants, including mercury, that occur during critical windows of neural development among genetically susceptible children (with a diminished capacity for metabolizing accumulated toxicants) may increase the risk for developmental disorders such as autism. Successfully identifying the specific combination of environmental exposures and genetic susceptibilities can inform the development of targeted prevention intervention strategies.

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  • February 12, 2008
Androgens / Encephalopathy / Glutathione / Immune / Mercury / Regression / Thimerosal / Toxicants

A case series of children with apparent mercury toxic encephalopathies manifesting with clinical symptoms of regressive autistic disorders

Excerpt:

“There was a significant dose-response relationship between the severity of the regressive ASDs observed and the total mercury dose children received from Thimerosal-containing vaccines/Rho (D)-immune globulin preparations. Based upon differential diagnoses, 8 of 9 patients examined were exposed to significant mercury from Thimerosal-containing biologic/vaccine preparations during their fetal/infant developmental periods, and subsequently, between 12 and 24 mo of age, these previously normally developing children suffered mercury toxic encephalopathies that manifested with clinical symptoms consistent with regressive ASDs. Evidence for mercury intoxication should be considered in the differential diagnosis as contributing to some regressive ASDs.”

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  • May 15, 2007

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