The role of glutathione in autism spectrum disorder (ASD) is emerging as a major topic, due to its role in the maintenance of the intracellular redox balance. Several studies have implicated glutathione redox imbalance as a leading factor in ASD, and both ASD and many other neurodevelopmental disorders involve low levels of reduced glutathione (GSH), high levels of oxidized glutathione (GSSG), and abnormalities in the expressions of glutathione-related enzymes in the blood or brain. Glutathione metabolism, through its impact on redox environment or redox-independent mechanisms, interferes with multiple mechanisms involved in ASD pathogenesis. Glutathione-mediated regulation of glutamate receptors [e.g., N-methyl-d-aspartate (NMDA) receptor], as well as the role of glutamate as a substrate for glutathione synthesis, may be involved in the regulation of glutamate excitotoxicity. However, the interaction between glutathione and glutamate in the pathogenesis of brain diseases may vary from synergism to antagonism. Modulation of glutathione is also associated with regulation of redox-sensitive transcription factors nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1) and downstream signaling (proinflammatory cytokines and inducible enzymes), thus providing a significant impact on neuroinflammation. Mitochondrial dysfunction, as well as neuronal apoptosis, may also provide a significant link between glutathione metabolism and ASD. Furthermore, it has been recently highlighted that glutathione can affect and modulate DNA methylation and epigenetics. Review analysis including research studies meeting the required criteria for analysis showed statistically significant differences between the plasma GSH and GSSG levels as well as GSH:GSSG ratio in autistic patients compared with healthy individuals (P = 0.0145, P = 0.0150 and P = 0.0202, respectively). Therefore, the existing data provide a strong background on the role of the glutathione system in ASD pathogenesis. Future research is necessary to investigate the role of glutathione redox signaling in ASD, which could potentially also lead to promising therapeutics.
According to the United States Centers for Disease Control and Prevention (CDC), as of July 11, 2016, the reported average incidence of children diagnosed with an autism spectrum disorder (ASD) was 1 in 68 (1.46%) among 8-year-old children born in 2004 and living within the 11 monitoring sites' surveillance areas in the United States of America (USA) in 2012. ASD is a multifaceted neurodevelopmental disorder that is also considered a hidden disability, as, for the most part; there are no apparent morphological differences between children with ASD and typically developing children. ASD is diagnosed based upon a triad of features including impairment in socialization, impairment in language, and repetitive and stereotypic behaviors. The increasing incidence of ASD in the pediatric population and the lack of successful curative therapies make ASD one of the most challenging disorders for medicine. ASD neurobiology is thought to be associated with oxidative stress, as shown by increased levels of reactive oxygen species and increased lipid peroxidation, as well as an increase in other indicators of oxidative stress. Children with ASD diagnosis are considered more vulnerable to oxidative stress because of their imbalance in intracellular and extracellular glutathione levels and decreased glutathione reserve capacity. Several studies have suggested that the redox imbalance and oxidative stress are integral parts of ASD pathophysiology. As such, early assessment and treatment of antioxidant status may result in a better prognosis as it could decrease the oxidative stress in the brain before it can induce more irreversible brain damage. In this review, many aspects of the role of oxidative stress in ASD are discussed, taking into account that the process of oxidative stress may be a target for therapeutic interventions.
- MeSH
- aerobióza MeSH
- antioxidancia metabolismus MeSH
- centrální nervový systém metabolismus MeSH
- dítě MeSH
- dysbióza komplikace MeSH
- gastrointestinální nemoci komplikace MeSH
- glutathionperoxidasa metabolismus MeSH
- incidence MeSH
- lidé MeSH
- metalothionein metabolismus MeSH
- mitochondrie metabolismus MeSH
- mozek - chemie MeSH
- neurodegenerativní nemoci etiologie metabolismus MeSH
- oxidace-redukce MeSH
- oxidační stres * MeSH
- peroxidace lipidů MeSH
- poruchy autistického spektra epidemiologie imunologie metabolismus patofyziologie MeSH
- předškolní dítě MeSH
- scavengery volných radikálů metabolismus MeSH
- selen fyziologie MeSH
- selenoproteiny metabolismus MeSH
- střevní mikroflóra MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Cobalt is an essential trace element that is known to mimic hypoxia and hypoxic training. Inorganic Co compounds are capable of Hypoxia-inducible factor-1 (HIF-1) activation, resulting in up-regulation of gene expression including erythropoietin (Epo). Experimental studies have demonstrated that Co treatment may increase hypoxic tolerance of different tissues, improve muscle metabolism and exercise performance. Other mechanisms may also involve modulation of steroid hormone and iron metabolism. Based on these experimental studies, in 2017 inorganic cobalt compounds were added into the World Anti-Doping Agency (WADA) prohibited list as doping agents. However, the existing data on beneficial effects of cobalt on exercise performance in athletes are scarce. Similarly, only experimental studies demonstrated exercise-induced decrease in tissue Co levels, whereas human data are inconsistent. In addition, multiple studies have demonstrated that excessive Co intake may be toxic due to prooxidant, proinflammatory, and proapoptotic activity. Therefore, monitoring of Co deficiency and overload is required to prevent potential health hazards in athletes. At the same time, modulation of Co status should be performed through supplementation avoiding excessive doses of inorganic cobalt that are used for doping and are accompanied by adverse health effects of metal toxicity.
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- doping ve sportu zákonodárství a právo MeSH
- dospělí MeSH
- erythropoetin biosyntéza fyziologie genetika MeSH
- fyzická vytrvalost účinky léků MeSH
- hypoxie chemicky indukované metabolismus MeSH
- kobalt * aplikace a dávkování metabolismus škodlivé účinky MeSH
- kosterní svaly fyziologie metabolismus účinky léků MeSH
- látky zvyšující výkon MeSH
- lidé MeSH
- tolerance léku genetika MeSH
- železo krev metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Purpose Investigation of the effect of exercise and zinc (Zn) supplementation on trace element status in rats. Methods 24 male Wistar were divided into four groups: control, exercised, Zn-supplemented (15 mg/kg weight Zn asparaginate), exercised Zn-supplemented. Zn was supplemented as Zn asparaginate. Serum lactate and creatinine levels, and creatine kinase activity were assessed. Tissue trace elements were estimated using inductively coupled plasma mass spectrometry. Results Exercise significantly increased lactate, and creatinine levels. Exercise significantly decreased muscle, kidney, and hair Zn; liver, muscle and serum Co; serum Fe; myocardial and hair Cu; liver, heart, skeletal muscle and kidney Se levels. Oppositely, exercise results in elevation of liver Zn; heart and skeletal muscle, kidney and hair Fe; kidney Cu; liver and hair Mn; serum and hair Se content. Zn supplementation reduced exercise-induced increase in lactate and creatinine levels, and elevated liver, kidney, heart, and hair Zn content in exercised rats. Supplementation with Zn reversed exercise-induced decrease in Co levels and increased Fe and Se stores in animals with high physical activity. Conclusions Beneficial effect of zinc supplementation in exercised organism may be associated not only with modulation of zinc status but regulation of other essential trace elements status and their biological effects.
- MeSH
- běh fyziologie MeSH
- hmotnostní spektrometrie MeSH
- játra anatomie a histologie chemie metabolismus MeSH
- kobalt metabolismus MeSH
- kosterní svaly anatomie a histologie chemie metabolismus MeSH
- kreatinin krev MeSH
- kreatinkinasa krev metabolismus MeSH
- laktáty krev MeSH
- ledviny anatomie a histologie chemie metabolismus MeSH
- modely u zvířat MeSH
- myokard chemie metabolismus chemie metabolismus MeSH
- pohybová aktivita fyziologie MeSH
- potkani Wistar MeSH
- selen metabolismus MeSH
- stopové prvky * metabolismus MeSH
- vlasy, chlupy chemie metabolismus MeSH
- železo metabolismus MeSH
- zinek aplikace a dávkování metabolismus MeSH
- Check Tag
- mužské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
