The role of glutathione redox imbalance in autism spectrum disorder: A review

Bjørklund, Geir; Tinkov, Alexey A.; Hosnedlová, Božena; Kizek, René; Ajsuvakova, Olga P.; Chirumbolo, Salvatore; Skalnaya, Margarita G.; Peana, Massimiliano; Dadar, Maryam; El‐Ansary, Afaf; Qasem, Hanan; Adams, James B.; Aaseth, Jan; Skalny, Anatoly V.

doi:10.1016/j.freeradbiomed.2020.07.017

Cited by 121 publications

(69 citation statements)

References 176 publications

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“…In their systematic review and meta-analysis, Zheng et al (2016) reported that people with ASD had higher plasma glutamate levels than the healthy controls. A recent synthesis of several studies have shown a significant reduction of one of the most important intracellular defensive components - glutathione (GSH), and an increase of its oxidized form - glutathione disulfide, in the plasma of the patients with ASD compared with controls (Bjørklund et al, 2020). Increased glutamate concentration and subcortical GABAergic imbalance may cause neural excitotoxicity leading to insufficient inhibition of the prefrontal cortex and hyper-responsivity of the amygdala (Matte et al, 2010; Siever, 2008).…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of N-acetylcysteine in autism spectrum disorders: A meta-analysis of randomized controlled trials

Lee

et al. 2020

Aust N Z J Psychiatry

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Objective: Currently, pharmaceutical treatment options for autism spectrum disorder are limited. Brain glutaminergic dysregulation is observed in autism spectrum disorder. N-acetylcysteine, which can be converted to glutathione and subsequently release glutamate into the extracellular space, and thus reduce glutamatergic neurotransmission at synapses, is considered a potential drug for autism spectrum disorder treatment. Here, we analyzed the treatment effects of N-acetylcysteine on autism spectrum disorder in randomized controlled trials. Study design: Updated systematic review and meta-analysis. Data sources: By systematically searching the PubMed, Embase and Cochrane Library, we obtained five randomized controlled trials. Study selection: Meta-analyses were performed to examine the improvement in autistic behaviors as measured by the Aberrant Behavior Checklist, Social Responsiveness Scale and Repetitive Behavior Scale–Revised, using mean difference with a 95% confidence interval and a random-effects model. Data Synthesis: After 8–12 weeks of N-acetylcysteine supplementation, the pooled result of four trials revealed an improvement in Aberrant Behavior Checklist total score (mean difference = 1.31, 95% confidence interval = [0.42, 2.20]). When one trial was excluded, the sensitivity test result was stronger (mean difference = 1.88, 95% confidence interval = [0.92, 2.83]). The pooled results of three trials revealed significant improvements in hyperactivity (mean difference = 4.80, 95% confidence interval = [1.20, 8.40]) and irritability (mean difference = 4.07, 95% confidence interval = [1.13, 7.04]). Regarding Social Responsiveness Scale, the pooled result of two trials showed significant improvement in social awareness after 8–12 weeks of N-acetylcysteine supplementation (mean difference = 1.34, 95% confidence interval = [0.09, 2.59]). No differences were observed in the pooled results of two trials using Repetitive Behavior Scale, either in the total or the subscales. Conclusion: We concluded that N-acetylcysteine is safe and tolerable, reduces hyperactivity and irritability and enhances social awareness in children with autism spectrum disorder. However, further evidence should be sought before a general recommendation.

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Section: Introductionmentioning

confidence: 99%

Effectiveness of N-acetylcysteine in autism spectrum disorders: A meta-analysis of randomized controlled trials

Lee

et al. 2020

Aust N Z J Psychiatry

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“…Integrates all exposure sources and absorption routes. Obviously, testing the exposure to elements should take into account the individual variability and its kinetics, in particular absorption, distribution, metabolism and excretion [18] [19]. The level of trace elements in hair re ects the average status of the body, assuming that hair grows at a rate of 1 cm per month.…”

Section: Teethmentioning

confidence: 99%

“…Low levels of reduced glutathione cause oxidative stress, which is an important factor in in ammation of the nervous system. In turn, the effect of low levels of reduced glutathione causes lower capability to eliminate toxic metals from the body, the consequence of which can be ASD [18].…”

Section: Toxic Elements and Asdmentioning

confidence: 99%

Hair Trace Elements in Children With Autism Spectrum Disorders: Systematic Literature Review

Mikulewicz

Chojnacka

2021

Preprint

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(1) Background: The aim of this work was to systematically review the literature on the relation between the levels of elements in hair (toxic elements and trace elements) on the occurrence of autism spectrum disorder. (2) Methods: Search strategy and study selection: Original articles were included if they met the including criteria that report the trace element levels in hair. The following databases were screened: Medline (via PubMed), Scopus, Web of Science, Google Scholar (from 2000.01.01 to 2020.11.11). The main search terms used were “hair element analysis and trace elements and autism”. (3) Results: The papers available describe results of studies undertaken with the use of different methodology: diversified size of experimental groups, different sampling and analytical techniques. Therefore direct comparison of the results is not informative. (4) Conclusions: It was found that pathogenesis of autism spectrum disorder was associated with the exposure to toxic elements (e.g. Hg and Pb) which act as neurotoxicants. Also, the relation between some microelements seem to be significant, in particular the ratio Zn/Cu. Higher level of zinc and level levels of copper play the protectory role.

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“…Glutathione exists in two forms-reduced (GSH) and oxidized (GSSG)-and the ratio of the two forms (GSSG/GSH) indicates the degree of oxidative stress in cells (Bjørklund et al, 2020). In biological reactions, GSH and GSSG can be converted into each other in the presence of enzymes (Figure 3).…”

Section: ) When the System X Cmentioning

confidence: 99%

“…GSH is also a substrate for GPX4, which converts GSH to GSSG. Adjusting the GSSG/GSH ratio affects ROS levels (Bjørklund et al, 2020;Capelletti et al, 2020). However, in epilepsy, the GSH level was decreased, and the ROS level was increased.…”

Section: ) When the System X Cmentioning

confidence: 99%

Iron Metabolism and Ferroptosis in Epilepsy

Chen

Zhang

et al. 2020

Front. Neurosci.

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Epilepsy is a disease characterized by recurrent, episodic, and transient central nervous system (CNS) dysfunction resulting from an excessive synchronous discharge of brain neurons. It is characterized by diverse etiology, complex pathogenesis, and difficult treatment. In addition, most epileptic patients exhibit social cognitive impairment and psychological impairment. Iron is an essential trace element for human growth and development and is also involved in a variety of redox reactions in organisms. However, abnormal iron metabolism is associated with several neurological disorders, including hemorrhagic post-stroke epilepsy and post-traumatic epilepsy (PTE). Moreover, ferroptosis is also considered a new form of regulation of cell death, which is attributed to severe lipid peroxidation caused by the production of reactive oxygen species (ROS) and iron overload found in various neurological diseases, including epilepsy. Therefore, this review summarizes the study on iron metabolism and ferroptosis in epilepsy, in order to elucidate the correlation between iron and epilepsy. It also provides a novel method for the treatment, prevention, and research of epilepsy, to control epileptic seizures and reduce nerve injury after the epileptic seizure.

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The role of glutathione redox imbalance in autism spectrum disorder: A review

Cited by 121 publications

References 176 publications

Effectiveness of N-acetylcysteine in autism spectrum disorders: A meta-analysis of randomized controlled trials

Effectiveness of N-acetylcysteine in autism spectrum disorders: A meta-analysis of randomized controlled trials

Hair Trace Elements in Children With Autism Spectrum Disorders: Systematic Literature Review

Iron Metabolism and Ferroptosis in Epilepsy

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