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Role of Oxidative Stress and Antioxidants in Autism

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Personalized Food Intervention and Therapy for Autism Spectrum Disorder Management

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 24))

Abstract

Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders with poorly understood etiology that are defined exclusively on the basis of behavioral observations. This disorder has been linked to increased levels of oxidative stress and lower antioxidant capacity. Oxidative stress in autism has been studied at the membrane level and also by measuring products of lipid peroxidation, detoxifying agents (such as glutathione), and antioxidants involved in the defense system against reactive oxygen species (ROS). Several studies have suggested alterations in the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and catalase in autism. Additionally, altered glutathione levels and homocysteine/methionine metabolism, increased inflammation, excitotoxicity, as well as mitochondrial and immune dysfunction have been suggested in autism. Moreover, environmental and genetic risk factors may intensify vulnerability to oxidative stress in autism. Collectively, these studies suggest increased oxidative stress in autism that may contribute to the development of this disease both in terms of pathogenesis and clinical symptoms. Antioxidant supplementation, or ways to improve the altered metabolite levels in the interconnected transmethylation and transsulfuration pathways, has been associated with decreased autistic behaviors and severity. This chapter provides a conceptual framework on oxidative stress and antioxidants utility. These types of interventions should be further studied in order to determine their effectiveness at improving metabolic imbalances.

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References

  1. Lopez-Alarcona, C., & Denicola, A. (2013). Evaluating the antioxidant capacity of natural products: A review on chemical and cellular-based assays. Analytica Chimica Acta, 763, 1–10.

    Article  Google Scholar 

  2. Sies, H. (1985). Oxidative stress: Introductory remarks. London: Academic Press.

    Google Scholar 

  3. Poljsak, B., Suput, D., & Milisav, I. (2013). Achieving the balance between ROS and antioxidants: When to use the synthetic antioxidants. Oxidative Medicine and Cellular Longevity, 2013, 956792.

    Article  Google Scholar 

  4. Koopman, W. J., Nijtmans, L. G., Dieteren, C. E., Roestenberg, P., Valsecchi, F., Smeitink, J. A. M., et al. (2010). Mammalian mitochondrial complex I: Biogenesis, regulation, and reactive oxygen species generation. Antioxidants & Redox Signaling, 12, 1431–1470.

    Article  CAS  Google Scholar 

  5. Kohen, R., & Nyska, A. (2002). Oxidation of biological systems: Oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification. Toxicologic Pathology, 30, 620–650.

    Article  CAS  Google Scholar 

  6. Gutteridge, J. M. C. (1994). Biological origin of free radicals, and mechanisms of antioxidant protection. Chemico-Biological Interactions, 91, 133–140.

    Article  CAS  Google Scholar 

  7. Berlett, B. S., & Stadtman, E. R. (1997). Protein oxidation in aging, disease, and oxidative stress. The Journal of Biological Chemistry, 272, 20313–20316.

    Article  CAS  Google Scholar 

  8. Poulsen, H. E., Specht, E., Broedbaek, K., Henriksen, T., Ellervik, C., MandrupPoulsen, T., et al. (2012). RNA modifications by oxidation: A novel disease mechanism. Free Radical Biology & Medicine, 52, 1353–1361.

    Article  CAS  Google Scholar 

  9. Yamamoto, H., Ozaki, T., Nakanishi, M., Kikuchi, H., Yoshida, K., Horie, H., et al. (2007). Oxidative stress induces p53-dependent apoptosis in hepatoblastoma cell through its nuclear translocation. Genes to Cells, 12, 461–471.

    Article  CAS  Google Scholar 

  10. Chu, F. F., Doroshow, J. H., & Esworthy, R. S. (1993). Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI. The Journal of Biological Chemistry, 268, 2571–2576.

    CAS  PubMed  Google Scholar 

  11. El-Agamey, A., Lowe, G. M., McGarvey, D. J., Mortensen, A., Phillip, D. M., Truscott, T. G., et al. (2004). Carotenoid radical chemistry and antioxidant/pro-oxidant properties. Arch Biochem Biophys, 430(1), 37–48.

    Google Scholar 

  12. Rose, S., Melnyk, S., Pavliv, O., Bai, S., Nick, T. G., Frye, R. E., et al. (2012). Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Translational Psychiatry, 2(7), 134.

    Article  Google Scholar 

  13. James, S. J., Melnyk, S., Jernigan, S., Pavliv, O., Trusty, T., Lehman, S., et al. (2010). A functional polymorphism in the reduced folate carrier gene and DNA hypomethylation in mothers of children with autism. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 153(6), 1209–1220.

    Google Scholar 

  14. Xie, W., Ge, X., Li, L., Yao, A., Wang, X., Li, M., et al. (2018). Resveratrol ameliorates prenatal progestin exposure-induced autism-like behavior through ERß activation. Molecular Autism, 2, 9–43.

    Google Scholar 

  15. Hamzawy, M. A., El-Ghandour, Y. B., Abdel-Aziem, S. H., & Ali, Z. H. (2018). Leptin and camel milk abate oxidative stress status, genotoxicity induced in valproic acid rat model of autism. International Journal of Immunopathology and Pharmacology, 32, 2058738418785514.

    Article  Google Scholar 

  16. Khalaj, R., Hajizadeh Moghaddam, A., & Zare, M. (2018). Hesperetin and it nanocrystals ameliorate social behavior deficits and oxido-inflammatory stress in rat model of autism. International Journal of Developmental Neuroscience, 69, 80–87.

    Article  CAS  Google Scholar 

  17. Frandsen, J. R., & Narayanasamy, P. (2018). Neuroprotection through flavonoid: Enhancement of the glyoxalase pathway. Redox Biology, 14, 465–473.

    Article  CAS  Google Scholar 

  18. Ahmad, S. F., Ansari, M. A., Nadeem, A., Bakheet, S. A., Alzahrani, M. Z., Alshammari, M. A., et al. (2018). Resveratrol attenuates pro-inflammatory cytokines and activation of JAK1-STAT3 in BTBR T+ Itpr3tf/J autistic mice. European Journal of Pharmacology, 829, 70–78.

    Article  CAS  Google Scholar 

  19. Ahmad, S. F., Ansari, M. A., Nadeem, A., Alzahrani, M. Z., Bakheet, S. A., & Attia, S. M. (2018). Resveratrol improves neuroimmune dysregulation through the inhibition of neuronal toll-like receptors and COX-2 signaling in BTBR T+ Itpr3tf/J mice. Neuromolecular Medicine, 20(1), 133–146.

    Article  CAS  Google Scholar 

  20. Rani, V., Gautam, S., Rawat, J. K., Singh, M., Devi, U., Yadav, R. K., et al. (2018). Effects of minocycline and doxycycline against terbutaline induced early postnatal autistic changes in albino rats. Physiology & Behavior, 183, 49–56.

    Article  CAS  Google Scholar 

  21. Zhang, Y., Cui, W., Zhai, Q., Zhang, T., & Wen, X. (2017). N-acetylcysteine ameliorates repetitive/stereotypic behavior due to its antioxidant properties without activation of the canonical Wnt pathway in a valproic acid-induced rat model of autism. Molecular Medicine Reports, 16(2), 2233–2240.

    Article  CAS  Google Scholar 

  22. Dominiak, A., Wilkaniec, A., Jesko, H., Czapski, G. A., Lenkiewicz, A. M., Kurek, E., et al. (2017). Selol, an organic selenium donor, prevents lipopolysaccharide-induced oxidative stress and inflammatory reaction in the rat brain. Neurochemistry International, 108, 66–77.

    Article  CAS  Google Scholar 

  23. Bhandari, R., & Kuhad, A. (2017). Resveratrol suppresses neuroinflammation in the experimental paradigm of autism spectrum disorders. Neurochemistry International, 103, 8–23.

    Article  CAS  Google Scholar 

  24. Gao, J., Wang, X., Sun, H., Cao, Y., Liang, S., Wang, H., et al. (2016). Neuroprotective effects of docosahexaenoic acid on hippocampal cell death and learning and memory impairments in a valproic acid-induced rat autism model. International Journal of Developmental Neuroscience, 49, 67–78.

    Article  CAS  Google Scholar 

  25. Khongrum, J., & Wattanathorn, J. (2015). Laser acupuncture improves behavioral disorders and brain oxidative stress status in the valproic acid rat model of autism. Journal of Acupuncture and Meridian Studies, 8(4), 183–191.

    Article  Google Scholar 

  26. Ayyathan, D. M., Chandrasekaran, R., & Thiagarajan, K. (2015). Neuroprotective effect of Tagara, an Ayurvedic drug against methyl mercury induced oxidative stress using rat brain mitochondrial fractions. BMC Complementary and Alternative Medicine, 15, 268.

    Article  Google Scholar 

  27. Zhang, Y., Yang, C., Yuan, G., Wang, Z., Cui, W., & Li, R. (2015). Sulindac attenuates valproic acid-induced oxidative stress levels in primary cultured cortical neurons and ameliorates repetitive/stereotypic-like movement disorders in Wistar rats prenatally exposed to valproic acid. International Journal of Molecular Medicine, 35(1), 263–270.

    Article  CAS  Google Scholar 

  28. Aldbass, A. M., Bhat, R. S., & El-Ansary, A. (2013). Protective and therapeutic potency of N-acetyl-cysteine on propionic acid-induced biochemical autistic features in rats. Journal of Neuroinflammation, 27, 10–42.

    Google Scholar 

  29. Sandhya, T., Sowjanya, J., & Veeresh, B. (2012). Bacopa monnieri (L.) Wettst ameliorates behavioral alterations and oxidative markers in sodium valproate induced autism in rats. Neurochemical Research, 37, 1121–1131.

    Article  CAS  Google Scholar 

  30. Sadek, A., Berk, L. S., Mainess, K., & Daher, N. S. (2018). Antioxidants and autism: Teachers’ perceptions of behavioral changes. Advances in Mind-Body Medicine, 32(3), 12–17.

    PubMed  Google Scholar 

  31. Bent, S., Lawton, B., Warren, T., Widjaja, F., Dang, K., Fahey, J. W., et al. (2018). Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli. Molecular Autism, 9, 35.

    Article  Google Scholar 

  32. Mousavinejad, E., Ghaffari, M. A., Riahi, F., Hajmohammadi, M., Tiznobeyk, Z., & Mousavinejad, M. (2018). Coenzyme Q10 supplementation reduces oxidative stress and decreases antioxidant enzyme activity in children with autism spectrum disorders. Psychiatry Research, 265, 62–69.

    Article  CAS  Google Scholar 

  33. Nikoo, M., Radnia, H., Farokhnia, M., Mohammadi, M. R., & Akhondzadeh, S. (2015). N-acetylcysteine as an adjunctive therapy to risperidone for treatment of irritability in autism: A randomized, double-blind, placebo-controlled clinical trial of efficacy and safety. Clinical Neuropharmacology, 38(1), 11–17.

    Article  CAS  Google Scholar 

  34. Al-Ayadhi, L. Y., & Elamin, N. E. (2013). Camel milk as a potential therapy as an antioxidant in autism spectrum disorder (ASD). Evidence-based Complementary and Alternative Medicine, 2013, 602834.

    Article  Google Scholar 

  35. Toroser, D., & Sohal, R. S. (2007). Age-associated perturbations in glutathione synthesis in mouse liver. The Biochemical Journal, 405(3), 583–589.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Chidambaram, Tamil Nadu, India

    Thamilarasan Manivasagam, Selvaraj Arunadevi & Arokiasamy Justin Thenmozhi

  2. Department of Food Science and Nutrition, CAMS, Sultan Qaboos University, Muscat, Oman

    Mustafa Mohamed Essa

  3. Ageing and Dementia Research Group, Sultan Qaboos University, Muscat, Oman

    Mustafa Mohamed Essa

  4. Food and Brain Research Foundation, Chennai, Tamil Nadu, India

    Mustafa Mohamed Essa

  5. Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research (JSSAHER), Mysuru, India

    Chidambaram SaravanaBabu

  6. Cellular and Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar, Assam, India

    Anupom Borah

  7. Research & Policy Department, World Innovation Summit for Health (WISH), Qatar Foundation, Doha, Qatar

    M. Walid Qoronfleh

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  1. Thamilarasan Manivasagam
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  2. Selvaraj Arunadevi
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Editors and Affiliations

  1. Food Science and Nutrition, CAMS, Sultan Qaboos University, Muscat, Oman

    M. Mohamed Essa

  2. World Innovation Summit for Health WISH, Qatar Foundation, Doha, Qatar

    M. Walid Qoronfleh

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Manivasagam, T. et al. (2020). Role of Oxidative Stress and Antioxidants in Autism. In: Essa, M., Qoronfleh, M. (eds) Personalized Food Intervention and Therapy for Autism Spectrum Disorder Management. Advances in Neurobiology, vol 24. Springer, Cham. https://doi.org/10.1007/978-3-030-30402-7_7

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