Oxidative Stress

Glial Cells / Inflammation / Neuroinflammation / Oxidative Stress / Toxicants

Large Brains in Autism: The Challenge of Pervasive Abnormality

Excerpt: “Oxidative stress, brain inflammation, and microgliosis have been much documented in association with toxic exposures including various heavy metals…the awareness that the brain as well as medical conditions of children with autism may be conditioned by chronic biomedical abnormalities such as inflammation opens the possibility that meaningful biomedical interventions may be possible well past the window of maximal neuroplasticity in early childhood because the basis for assuming that all deficits can be attributed to fixed early developmental alterations in neural architecture has now been undermined.”

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  • June 29, 2016
20 Papers / CDC / Glutamate / Glutathione / Mercury / Oxidative Stress / Review / Thimerosal / Toxicants

Mercury-Induced Toxicity: Multiple Mechanisms of Action

Excerpts:
“The difference in manifested toxicity of MeHg and EtHg are likely the result of the differences in exposure, metabolism, and elimination from the body, rather than differences in mechanisms of action between the two.”

“Summary and Conclusions

There are many commonalities/similarities in the mechanisms of toxic action of methylmercury and ethylmercury (from thimerosal)… Evidence for the similarity of the various mechanisms of toxicity include the following:

• Both MeHg and EtHg bind to the amino acid cysteine (Clarkson 1995; Wu et al. 2008)…

• Both decrease glutathione activity, thus providing less protection from the oxidative stress caused by MeHg and EtHg (Carocci et al. 2014; Ndountse and Chan (2008); Choi et al. 1996; Franco et al. 2006; Mori et al. 2007; Muller et al. 2001; Ndountse and Chan 2008; Wu et al. 2008)…

• Both disrupt glutamate homeostasis (Farina et al. 2003a, b; Manfroi et al. 2004; Mutkus et al. 2005; Yin et al. 2007).

• Both cause oxidative stress/creation of ROS (Dreiem and Seegal 2007; Garg and Chang 2006; Myhre et al. 2003; Sharpe et al. 2012; Yin et al. 2007)…

• Both cause effects on receptor binding/neurotransmitter release involving one or more transmitters (Basu et al. 2008; Coccini et al. 2000; Cooper et al. 2003; Fonfria et al. 2001; Ida-Eto et al. 2011; Ndountse and Chan 2008; Yuan and Atchison 2003).

• Both cause DNA damage or impair DNA synthesis (Burke et al. 2006; Sharpe et al. 2012; Wu et al. 2008).”

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  • January 1, 2016
Aluminum / Autism Biomarkers / Glial Cells / Inflammation / Lipids / Mercury / Mitochondria / Neuroinflammation / Oxidative Stress / Thimerosal / Toxicants

Biomarkers in Autism

Abstract

Autism spectrum disorders (ASDs) are complex, heterogeneous disorders caused by an interaction between genetic vulnerability and environmental factors. In an effort to better target the underlying roots of ASD for diagnosis and treatment, efforts to identify reliable biomarkers in genetics, neuroimaging, gene expression, and measures of the body’s metabolism are growing. For this article, we review the published studies of potential biomarkers in autism and conclude that while there is increasing promise of finding biomarkers that can help us target treatment, there are none with enough evidence to support routine clinical use unless medical illness is suspected. Promising biomarkers include those for mitochondrial function, oxidative stress, and immune function. Genetic clusters are also suggesting the potential for useful biomarkers.

Excerpt: “A recent review assessed the research on physiological abnormalities associated with ASD (44). The authors identified four main mechanisms that have been increasingly studied during the past decade: immunologic/inflammation, oxidative stress, environmental toxicants, and mitochondrial abnormalities. In addition, there is accumulating research on the lipid, GI systems, microglial activation, and the microbiome, and how these can also contribute to generating biomarkers associated with ASD (45, 46).

Pathways are interconnected with a defect in one likely leading to dysfunction in others. Many metabolic disorders can lead to endpoints such as impaired methylation, sulfuration, and detoxification pathways and nutritional deficiencies. Mitochondrial dysfunction, environmental risk factors, metabolic imbalances, and genetic susceptibility can all lead to oxidative stress (47), which in turn leads to inflammation, damaged cell membranes, autoimmunity (48), impaired methylation (49), cell death (48), and neurological deficits (50). The brain is highly vulnerable to oxidative stress (51), particularly in children (52) during the early part of development (47). As environmental events and metabolic imbalances affect oxidative stress and methylation, they also can affect the expression of genes.”

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  • August 12, 2014
GI / Oxidative Stress

Enrichment of Elevated Plasma F2t-Isoprostane Levels in Individuals with Autism Who Are Stratified by Presence of Gastrointestinal Dysfunction

Excerpt:
“Elevation in peripheral oxidative stress is consistent with, and may contribute to, the more severe functional impairments in the ASD-GID group. With unique medical, metabolic, and behavioral features in children with ASD-GID, the present findings serve as a compelling rationale for both individualized approaches to clinical care and integrated studies of biomarker enrichment in ASD subgroups that may better address the complex etiology of ASD.”

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  • July 3, 2013
Autism Biomarkers / Glutathione / Homocysteine / Methionine / Methylation / Oxidative Stress / Thioredoxin / Transsulfuration

Newborn screening for autism: in search of candidate biomarkers

Excerpts:

“GST [Glutathione S-transferase] is a metabolic biomarker directly associated with ASD. The human gene product for GST constitutes a candidate susceptibility protein due to its tissue distribution and role in oxidative stress and methionine metabolism, which results in neuronal injury and death.”

“Results of a recent study further demonstrated that glutathione, total glutathione and activity levels of GST were significantly lower in autistic patients as compared with control subjects; however, homocysteine, thioredoxin reductase and perioxidoxin levels were remarkably higher.”

“Autistic children with metabolic disturbances are known to display reduced metabolic activities of GST, cysteine, glutathione and methionine, which are associated with methionine transmethylation and trans-sulfation.”

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  • April 16, 2013
Astrocytes / Mercury / Mitochondria / mtDNA / Oxidative Stress / Thimerosal / Toxicants

Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA

Abstract
Thimerosal generates ethylmercury in aqueous solution and is widely used as preservative. We have investigated the toxicology of Thimerosal in normal human astrocytes, paying particular attention to mitochondrial function and the generation of specific oxidants. We find that ethylmercury not only inhibits mitochondrial respiration leading to a drop in the steady state membrane potential, but also concurrent with these phenomena increases the formation of superoxide, hydrogen peroxide, and Fenton/Haber-Weiss generated hydroxyl radical. These oxidants increase the levels of cellular aldehyde/ketones. Additionally, we find a five-fold increase in the levels of oxidant damaged mitochondrial DNA bases and increases in the levels of mtDNA nicks and blunt-ended breaks. Highly damaged mitochondria are characterized by having very low membrane potentials, increased superoxide/hydrogen peroxide production, and extensively damaged mtDNA and proteins. These mitochondria appear to have undergone a permeability transition, an observation supported by the five-fold increase in Caspase-3 activity observed after Thimerosal treatment.

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  • June 28, 2012
Glutathione / Inflammation / Methylation / Neuroinflammation / Oxidative Stress / Review / ROS

Glutathione-Related Factors and Oxidative Stress in Autism, A Review

Excerpts:
“The current literature suggests an imbalance of oxidative and anti-oxidative stress systems in autism. Glutathione is involved in neuro-protection against oxidative stress and neuro-inflammation in autism by improving the anti-oxidative stress system. Decreasing the oxidative stress might be a potential treatment for autism.”

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  • February 20, 2012

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