scholarly journals Nrf2 Activators as Dietary Phytochemicals Against Oxidative Stress, Inflammation, and Mitochondrial Dysfunction in Autism Spectrum Disorders: A Systematic Review

2020 ◽  
Vol 11 ◽  
Author(s):  
Jiaxin Yang ◽  
Xi Fu ◽  
Xiaoli Liao ◽  
Yamin Li
Keyword(s):  
Oxidative Stress ◽  
Systematic Review ◽  
Mitochondrial Dysfunction ◽  
Clinical Studies ◽  
Autism Spectrum ◽  
Research Progress ◽  
Current Evidence ◽  
Preclinical Studies ◽  
Dietary Phytochemicals ◽  
Nrf2 Activator

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder with limited available treatments and diverse causes. In ASD patients, numerous researches demonstrated various alterations in inflammation/immune, oxidative stress, and mitochondrial dysfunction, and these alterations could be regulated by Nrf2. Hence, we aimed to systematically review the current evidence about the effects of Nrf2 activator supplementation on ASD objects from in vitro studies, animal studies, and clinical studies. Relevant articles were retrieved through searching for the Cochrane Library, PubMed, Web of Science, Scope, Embase, and CNKI databases (through September 23, 2020). Ultimately, we identified 22 preclinical studies, one cell culture study, and seven clinical studies, covering a total of five Nrf2 activators. For each Nrf2 activator, we focused on its definition, potential therapeutic mechanisms, latest research progress, research limitations, and future development directions. Our systematic review provided suggestive evidence that Nrf2 activators have a potentially beneficial role in improving autism-like behaviors and abnormal molecular alterations through oxidant stress, inflammation, and mitochondrial dysfunction. These dietary phytochemicals are considered to be relatively safer and effective for ASD treatment. However, there are few clinical studies to support the Nrf2 activators as dietary phytochemicals in ASD, even though several preclinical studies. Therefore, caution should be warranted in attempting to extrapolate their effects in human studies, and better design and more rigorous research are required before they can be determined as a therapeutic option.

scholarly journals Relationship between Autism Spectrum Disorder and Pesticides: A Systematic Review of Human and Preclinical Models

2021 ◽  
Vol 18 (10) ◽  
pp. 5190
Author(s):  
Judit Biosca-Brull ◽  
Cristian Pérez-Fernández ◽  
Santiago Mora ◽  
Beatriz Carrillo ◽  
Helena Pinos ◽  
...  
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorder ◽  
Experimental Studies ◽  
Clinical Signs ◽  
Epidemiological Studies ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Preclinical Studies ◽  
Preclinical Models ◽  
Gestational Exposure

Autism spectrum disorder (ASD) is a complex set of neurodevelopmental pathologies characterized by impoverished social and communicative abilities and stereotyped behaviors. Although its genetic basis is unquestionable, the involvement of environmental factors such as exposure to pesticides has also been proposed. Despite the systematic analyses of this relationship in humans, there are no specific reviews including both human and preclinical models. The present systematic review summarizes, analyzes, and discusses recent advances in preclinical and epidemiological studies. We included 45 human and 16 preclinical studies. These studies focused on Organophosphates (OP), Organochlorine (OC), Pyrethroid (PT), Neonicotinoid (NN), Carbamate (CM), and mixed exposures. Preclinical studies, where the OP Chlorpyrifos (CPF) compound is the one most studied, pointed to an association between gestational exposure and increased ASD-like behaviors, although the data are inconclusive with regard to other ages or pesticides. Studies in humans focused on prenatal exposure to OP and OC agents, and report cognitive and behavioral alterations related to ASD symptomatology. The results of both suggest that gestational exposure to certain OP agents could be linked to the clinical signs of ASD. Future experimental studies should focus on extending the analysis of ASD-like behaviors in preclinical models and include exposure patterns similar to those observed in human studies.

scholarly journals Efficacy and safety of microbiota transfer therapy for the management of autism spectrum disorder in children: a systematic review

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 48
Author(s):  
Pablo Daniel Estrella Porter ◽  
Luis Eduardo Guzmán Freire ◽  
Joseth Paulina Adatty Molina ◽  
María Verónica Burneo Raza ◽  
Henry Alejandro Carrión Celi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorder ◽  
Intervention Group ◽  
Autism Spectrum ◽  
Nervous System Development ◽  
Spectrum Disorder ◽  
Current Evidence ◽  
Cochrane Library ◽  
Efficacy And Safety ◽  
Level Of Evidence

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with an unclear etiologic mechanism. Following suggestions in the literature of a close relation between the gut microbiota and the central nervous system development, neuroimmune and neuroendocrine systems, new theories and strategies of the management of ASD in children focus on the brain-gut axis via microbiota transfer therapy. Despite the regular appearance in the news, the level of evidence supporting this intervention is unclear and to this date, no systematic review on this issue has been published. Methods: We conducted a systematic literature review of the efficacy and safety of microbiota transfer therapy for the management of ASD in children. MEDLINE via PubMed, LILACS IBECS via BVS, EMBASE via Ovid, Scopus and Cochrane Library were searched on 19th April 2018. Results: One single study published in 2017 was identified. The intervention group included 18 patients and showed significant clinical improvements in the gastrointestinal and ASD-related symptoms. The clinical procedure was reported as safe and well-tolerated with some transitory adverse effects. Conclusions: The causality and correlation of the intervention and the expected outcomes cannot be assumed with current evidence. In addition, recommendations about the effectiveness or safety of microbiota transfer therapy in children with ASD cannot be currently issued. Randomized controlled trials and clinical protocols for the intervention are needed.

Preclinical studies conducted on nanozyme antioxidants: shortcomings and challenges based on US FDA regulations

Nanomedicine ◽  
2021 ◽  
Author(s):  
Milad Ghorbani ◽  
Zhila Izadi ◽  
Samira Jafari ◽  
Eudald Casals ◽  
Foroogh Rezaei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Trials ◽  
Clinical Studies ◽  
In Vivo Studies ◽  
Preclinical Studies ◽  
Future Studies ◽  
Clinical Stages ◽  
Us Fda ◽  
Considerable Body

The wide prevalence of oxidative stress-induced diseases has led to a growing demand for antioxidant therapeutics worldwide. Nanozyme antioxidants are drawing enormous attention as practical alternatives for conventional antioxidants. The considerable body of research over the last decade and the promising results achieved signify the potential of nanozyme antioxidants to secure a place in the expanding market of antioxidant therapeutics. Nonetheless, there is no report on clinical trials for their further evaluation. Through analyzing in-depth selected papers which have conducted in vivo studies on nanozyme antioxidants, this review aims to pinpoint and discuss possible reasons impeding development of research toward clinical studies and to offer some practical solutions for future studies to bridge the gap between preclinical and clinical stages.

scholarly journals Sex, Oxidative Stress, and Hypertension: Insights From Animal Models

Physiology ◽  
2019 ◽  
Vol 34 (3) ◽  
pp. 178-188 ◽  
Author(s):  
Jane F. Reckelhoff ◽  
Damian G. Romero ◽  
Licy L. Yanes Cardozo
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Animal Models ◽  
Blood Pressure Control ◽  
Clinical Studies ◽  
Pressure Control ◽  
Pharmacological Intervention ◽  
Preclinical Studies ◽  
Initial Development ◽  
And Oxidative Stress

One of the mechanisms responsible for blood pressure (BP) regulation is thought to be oxidative stress. In this review, we highlight preclinical studies that strongly support a role for oxidative stress in development and maintenance of hypertension in male animals, based on depressor responses to antioxidants, particularly tempol and apocynin. In females, oxidative stress seems to be important in the initial development of hypertension. However, whether maintenance of hypertension in females is mediated by oxidative stress is not clear. In clinical studies, pharmacological intervention to reduce BP with antioxidants has conflicting results, mostly negative. This review will discuss the uncertainties regarding blood pressure control and oxidative stress and potential reasons for these outcomes.

scholarly journals Targeting Inflammatory-Mitochondrial Response in Major Depression: Current Evidence and Further Challenges

2020 ◽  
Vol 2020 ◽  
pp. 1-20 ◽  
Author(s):  
Ana Paula Vargas Visentin ◽  
Rafael Colombo ◽  
Ellen Scotton ◽  
Débora Soligo Fracasso ◽  
Adriane Ribeiro da Rosa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Coenzyme Q ◽  
Antioxidant Defenses ◽  
Current Evidence ◽  
Stress Studies ◽  
Neuronal Membranes ◽  
Mitochondrial Membrane Depolarization ◽  
Depressive Patients ◽  
And Oxidative Stress

The prevalence of psychiatric disorders has increased in recent years. Among existing mental disorders, major depressive disorder (MDD) has emerged as one of the leading causes of disability worldwide, affecting individuals throughout their lives. Currently, MDD affects 15% of adults in the Americas. Over the past 50 years, pharmacotherapy, psychotherapy, and brain stimulation have been used to treat MDD. The most common approach is still pharmacotherapy; however, studies show that about 40% of patients are refractory to existing treatments. Although the monoamine hypothesis has been widely accepted as a molecular mechanism to explain the etiology of depression, its relationship with other biochemical phenomena remains only partially understood. This is the case of the link between MDD and inflammation, mitochondrial dysfunction, and oxidative stress. Studies have found that depressive patients usually exhibit altered inflammatory markers, mitochondrial membrane depolarization, oxidized mitochondrial DNA, and thus high levels of both central and peripheral reactive oxygen species (ROS). The effect of antidepressants on these events remains unclear. Nevertheless, the effects of ROS on the brain are well known, including lipid peroxidation of neuronal membranes, accumulation of peroxidation products in neurons, protein and DNA damage, reduced antioxidant defenses, apoptosis induction, and neuroinflammation. Antioxidants such as ascorbic acid, tocopherols, and coenzyme Q have shown promise in some depressive patients, but without consensus on their efficacy. Hence, this paper provides a review of MDD and its association with inflammation, mitochondrial dysfunction, and oxidative stress and is aimed at thoroughly discussing the putative links between these events, which may contribute to the design and development of new therapeutic approaches for patients.

scholarly journals Mesenchymal Stem Cell Therapy in Stroke: A Systematic Review of Literature in Pre-Clinical and Clinical Research

2018 ◽  
Vol 27 (12) ◽  
pp. 1723-1730 ◽  
Author(s):  
Haiqing Zheng ◽  
Bin Zhang ◽  
Pratik Y. Chhatbar ◽  
Yi Dong ◽  
Ali Alawieh ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Clinical Studies ◽  
Animal Studies ◽  
Current Evidence ◽  
Human Trials

Exogenous stem cell therapy (SCT) has been recognized recently as a promising neuroregenerative strategy to augment recovery in stroke survivors. Mesenchymal stem cells (MSCs) are the primary source of stem cells used in the majority of both pre-clinical and clinical studies in stroke. In the absence of evidence-based guidelines on the use of SCT in stroke patients, understanding the progress of MSC research across published studies will assist researchers and clinicians in better achieving success in translating research. We conducted a systematic review on published literature using MSCs in both pre-clinical studies and clinical trials between 2008 and 2017 using the public databases PubMed and Ovid Medline, and the clinical trial registry ( www.clinicaltrials.gov ). A total of 78 pre-clinical studies and eight clinical studies were identified. While majority of the pre-clinical and clinical studies demonstrated statistically significant effects, the clinical significance of these findings was still unclear. Effect sizes could not be measured mainly due to reporting issues in pre-clinical studies, thus limiting our ability to compare results across studies quantitatively. The overall quality of both pre-clinical and clinical studies was sub-optimal. By conducting a systematic review of both pre-clinical and clinical studies on MSCs therapy in stroke, we assessed the quality of current evidence and identified several issues and gaps in translating animal studies to human trials. Addressing these issues and incorporating changes into future animal studies and human trials may lead to better success of stem cells-based therapeutics in the near future.

scholarly journals Antioxidant and Anti-Inflammatory Effects of Genus Gynura: A Systematic Review

2020 ◽  
Vol 11 ◽  
Author(s):  
Jiah Ning Tan ◽  
Shamin Mohd Saffian ◽  
Fhataheya Buang ◽  
Zakiah Jubri ◽  
Ibrahim Jantan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Systematic Review ◽  
Clinical Studies ◽  
Glycogen Synthase ◽  
Chemical Constituents ◽  
Future Research ◽  
Prostaglandin E ◽  
Pharmacokinetic Studies ◽  
Related Factor ◽  
Anti Inflammatory

Background:Gynura species have been used traditionally to treat various ailments, such as fever, pain, and to control blood glucose level. This systematic review critically discusses studies regarding Gynura species that exhibited antioxidant and anti-inflammatory effects, thus providing perspectives and instructions for future research of the plants as a potential source of new dietary supplements or medicinal agents.Methods: A literature search from internet databases of PubMed, Scopus, Science Direct, e-theses Online Service, and ProQuest was carried out using a combination of keywords such as “Gynura,” “antioxidant,” “anti-inflammatory,” or other related words. Research articles were included in this study if they were experimental (in vitro and in vivo) or clinical studies on the antioxidant or anti-inflammatory effects of Gynura species and if they were articles published in English.Results: Altogether, 27 studies on antioxidant and anti-inflammatory effects of Gynura species were selected. The antioxidant effects of Gynura species were manifested by inhibition of reactive oxygen species production and lipid peroxidation, modulation of glutathione-related parameters, and enzymatic antioxidant production or activities. The anti-inflammatory effects of Gynura species were through the modulation of inflammatory cytokine production, inhibition of prostaglandin E2 and nitric oxide production, cellular inflammatory-related parameters, and inflammation in animal models. The potential anti-inflammatory signaling pathways modulated by Gynura species are glycogen synthase kinase-3, nuclear factor erythroid 2-related factor 2, PPARγ, MAPK, NF-κB, and PI3K/Akt. However, most reports on antioxidant and anti-inflammatory effects of the plants were on crude extracts, and the chemical constituents contributing to bioactivities were not clearly understood. There is a variation in quality of studies in terms of design, conduct, and interpretation, and in-depth studies on the underlying mechanisms involved in antioxidant and anti-inflammatory effects of the plants are in demand. Moreover, there is limited clinical study on antioxidant and anti-inflammatory effects of Gynura species.Conclusion: This review highlighted antioxidant and anti-inflammatory effects of genus Gynura and supported their traditional uses to treat oxidative stress and inflammatory-related diseases. This review is expected to catalyze further studies on genus Gynura. However, extensive preclinical data need to be generated from toxicity and pharmacokinetic studies before clinical studies can be pursued for their development into clinical medicines to treat oxidative stress and inflammatory conditions.

scholarly journals Increased Susceptibility to Ethylmercury-Induced Mitochondrial Dysfunction in a Subset of Autism Lymphoblastoid Cell Lines

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Shannon Rose ◽  
Rebecca Wynne ◽  
Richard E. Frye ◽  
Stepan Melnyk ◽  
S. Jill James
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Cell Lines ◽  
Autism Spectrum ◽  
Reserve Capacity ◽  
Flux Analysis ◽  
Lymphoblastoid Cell Lines ◽  
Extracellular Flux ◽  
Respiratory Parameters ◽  
Increased Risk

The association of autism spectrum disorders with oxidative stress, redox imbalance, and mitochondrial dysfunction has become increasingly recognized. In this study, extracellular flux analysis was used to compare mitochondrial respiration in lymphoblastoid cell lines (LCLs) from individuals with autism and unaffected controls exposed to ethylmercury, an environmental toxin known to deplete glutathione and induce oxidative stress and mitochondrial dysfunction. We also tested whether pretreating the autism LCLs with N-acetyl cysteine (NAC) to increase glutathione concentrations conferred protection from ethylmercury. Examination of 16 autism/control LCL pairs revealed that a subgroup (31%) of autism LCLs exhibited a greater reduction in ATP-linked respiration, maximal respiratory capacity, and reserve capacity when exposed to ethylmercury, compared to control LCLs. These respiratory parameters were significantly elevated at baseline in the ethylmercury-sensitive autism subgroup as compared to control LCLs. NAC pretreatment of the sensitive subgroup reduced (normalized) baseline respiratory parameters and blunted the exaggerated ethylmercury-induced reserve capacity depletion. These findings suggest that the epidemiological link between environmental mercury exposure and an increased risk of developing autism may be mediated through mitochondrial dysfunction and support the notion that a subset of individuals with autism may be vulnerable to environmental influences with detrimental effects on development through mitochondrial dysfunction.

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