Impact of Oxidative Stress on Jordanian Children with Autism Spectrum Disorder

Authors

  • Amal Al-Ramahi Faculty of Medical Allied Sciences, Al-Ahliyya Amman University, Amman, Jordan
  • Zainab Zakaraya Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan
  • Lina AlTamimi Faculty of Pharmacy, Zarqa University, Zarqa, Jordan
  • Mohammad Hailat Faculty of pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan https://orcid.org/0000-0003-4263-0134
  • Mohammed F Hamad Department of Basic Medical Sciences, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, Jordan
  • Wael Abu Dayyih Faculty of Pharmacy , Mutah University Al-Karak, Jordan
  • Ibrahim Alabbadi Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman, Jordan
  • Yousef AlRaoush Director of Psychiatric, Mental and Cognitive Behavioural Therapy Clinics, Amman, Jordan
  • Laila Al-Omari Department of Medical Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman, Jordan
  • Khaled Abdul-Aziz Ahmed Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan
  • Ala A Alhusban Faculty of pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan

DOI:

https://doi.org/10.35516/jjps.v18i3.2625

Keywords:

Autism Spectrum Disorder, Jordanian children, Glutathione Peroxidase, Superoxide Dismutase, Malondialdehyde, ADHD, anxiety, epilepsy, oxidative stress

Abstract

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder whose etiology is still unknown and without clinical biomarkers. Recent studies have highlighted the potential role of oxidative stress and metabolic changes in ASD. However, little is known about these changes in the Jordanian ASD population.

Aims: This study aimed to evaluate oxidative stress biomarkers in Jordanian children with ASD and to investigate the potential correlations with the disorder's clinical features.

Methodology: This cross-sectional study involved 80 Jordanian children divided into two groups: the patients’ group (diagnosed with ASD, n=40) and the control group (healthy, n=40). The study examined the distribution of ASD among the participants and assessed the prevalence of comorbid conditions. It also evaluated oxidative stress biomarkers, including Glutathione Peroxidase (GPX), Superoxide Dismutase (SOD), and Malondialdehyde (MDA).

Results: ASD was more common in males (65% in the ASD group) and in people with a family history of the disorder (55%). Common comorbid conditions included ADHD (42.5%), anxiety (25%), and epilepsy (15%). Children with ASD had significantly lower levels of GPX (2.72 ± 0.9 pmol/mL vs. 7.74 ± 2.5 pmol/mL in controls, p<0.005) and SOD (1.74 ± 0.75 ng/mL vs. 2.93 ± 0.98 ng/mL in controls, p<0.005) and higher levels of MDA (16 ± 1.95 nmol/mL vs. 5.46 ± 1.57 nmol/mL in controls, p<0.005).

Conclusion: This study suggests a potential association between ASD and oxidative stress. While further research is required, these findings contribute to our understanding of ASD pathogenesis and may guide future diagnostic and therapeutic approaches. Pearson correlation coefficients imply that increased oxidative stress, as measured by lower GPX and SOD levels and higher MDA levels, may be linked to the severity and presence of clinical features in ASD.

References

Hodges H., Fealko C., Soares N. Autism spectrum disorder: definition, epidemiology, causes, and clinical evaluation. Translational Pediatrics. 2020; 9(Suppl 1):S55–S65. https://doi.org/10.21037/tp.2019.09.09 DOI: https://doi.org/10.21037/tp.2019.09.09

Wahdan M.M., Malak M.Z., Al-Amer R., Ayed A., Russo S., Berte D.Z. Effect of Incredible Years autism spectrum and language delays (IY-ASD) program on stress and behavioral management skills among parents of children with autism spectrum disorder in Palestine. Journal of Pediatric Nursing. 2023; 72:45–52. https://doi.org/10.1016/j.pedn.2023.03.018 DOI: https://doi.org/10.1016/j.pedn.2023.03.018

Amman A.Z.U. Do close relative marriages contribute to the causes of autism among ethnic groups in Jordan, psychological effect on society? Journal of Education and Practice (Online). 2015; 5(12):1–6. Available from: www.iiste.org

Hyassat M., Al-Makahleh A., Rahahleh Z., Al-Zyoud N. The diagnostic process for children with autism spectrum disorder: a preliminary study of Jordanian parents’ perspectives. Children (Basel). 2023; 10(8):1394. https://doi.org/10.3390/children10081394 DOI: https://doi.org/10.3390/children10081394

Hirota T., King B.H. Autism Spectrum Disorder: A Review. JAMA. 2023; 329(2):157–168.

https://doi.org/10.1001/jama.2022.23661 DOI: https://doi.org/10.1001/jama.2022.23661

Al-Shayea Q., Al-Ani M. Biometric face recognition based on enhanced histogram approach. International Journal of Communication Networks and Information Security. 2018; 10(1):148–154.

https://doi.org/10.17762/ijcnis.v10i1.3142 DOI: https://doi.org/10.17762/ijcnis.v10i1.3142

Baio J., Wiggins L., Christensen D.L., Maenner M.J., Daniels J., Warren Z., Kurzius-Spencer M., Zahorodny W., Robinson Rosenberg C., White T., Durkin M.S., Imm P., Nikolaou L., Yeargin-Allsopp M., Lee L.-C., Harrington R., Lopez M., Fitzgerald R.T., Hewitt A., … Dowling N.F. Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years—Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014. Morbidity and Mortality Weekly Report. Surveillance Summaries. 2018; 67(6):1–23. https://doi.org/10.15585/mmwr.ss6706a1 DOI: https://doi.org/10.15585/mmwr.ss6706a1

Zeidan J., Fombonne E., Scorah J., Ibrahim A., Durkin M.S., Saxena S., Yusuf A., Shih A., Elsabbagh M. Global prevalence of autism: A systematic review update. Autism Research. 2022; 15(5):778–790. https://doi.org/10.1002/aur.2696 DOI: https://doi.org/10.1002/aur.2696

Liu X., Lin J., Zhang H., Khan N.U., Zhang J., Tang X., Cao X., Shen L. Oxidative stress in autism spectrum disorder—Current progress of mechanisms and biomarkers. Frontiers in Psychiatry. 2022; 13:813304. https://doi.org/10.3389/fpsyt.2022.813304

Farah A.I., Ahmad M.N., Al-Qirim T.M. The antioxidant and pro-oxidant impacts of varying levels of alpha-lipoic acid on biomarkers of myoglobin oxidation in vitro. Jordan Journal of Agricultural Sciences. 2020; 16(4):89–99. https://doi.org/10.35516/jjas.v16i4.63 DOI: https://doi.org/10.35516/jjas.v16i4.63

Hammad A.M., Shawaqfeh B., Hikmat S., Al-Qirim T., Hamadneh L., Al-Kouz S., Awad M.M., Hall F.S. The role of vitamin E in protecting against oxidative stress, inflammation, and the neurotoxic effects of acute paracetamol in pregnant female rats. Toxics. 2023; 11(4):368. https://doi.org/10.3390/toxics11040368 DOI: https://doi.org/10.3390/toxics11040368

Yao F., Zhang K., Feng C., Gao Y., Shen L., Liu X., Ni J. Protein biomarkers of autism spectrum disorder identified by computational and experimental methods. Frontiers in Psychiatry. 2021; 12:554621.

https://doi.org/10.3389/fpsyt.2021.554621 DOI: https://doi.org/10.3389/fpsyt.2021.554621

Rylaarsdam L., Guemez-Gamboa A. Genetic causes and modifiers of autism spectrum disorder. Frontiers in Cellular Neuroscience. 2019; 13:385.

https://doi.org/10.3389/fncel.2019.00385 DOI: https://doi.org/10.3389/fncel.2019.00385

Baxter A.J., Brugha T.S., Erskine H.E., Scheurer R.W., Vos T., Scott J.G. The epidemiology and global burden of autism spectrum disorders. Psychological Medicine. 2015; 45(3):601–613.

https://doi.org/10.1017/S003329171400172X DOI: https://doi.org/10.1017/S003329171400172X

Alhawmdeh E.H., Bulatova N.R., Yousef A.M.F., Alabbadi M.A., Omer E.A. A cross-sectional study of the catalase genetic polymorphism (-262 cytosine/thymine) and blood catalase activity among Jordanian vitiligo patients. Jordan Journal of Pharmaceutical Sciences. 2023; 16(2):330–344. https://doi.org/10.35516/jjps.v16i2.438 DOI: https://doi.org/10.35516/jjps.v16i2.438

Martinvalet D., Walch M. Editorial: The role of reactive oxygen species in protective immunity. Frontiers in Immunology. 2022; 12. DOI: https://doi.org/10.3389/fimmu.2021.832946

Gammoh O., Aburubaiha Z., Mayyas A., Alkatib W., Masarweh R., Elhajji F., Alqudah A. Valerian and hops combination versus escitalopram in models of depression and anxiety: A cross-talk with oxidative stress. Jordan Journal of Pharmaceutical Sciences. 2023; 16(1):124–136.

https://doi.org/10.35516/jjps.v16i1.1073 DOI: https://doi.org/10.35516/jjps.v16i1.1073

Al-Qirim T., Jasim S., Shawaqfeh B. Neurotoxic effect of paracetamol on female rats: Role of antioxidant treatment and prevention. The FASEB Journal. 2020; 34(S1):1. https://doi.org/10.1096/fasebj.2020.34.s1.00116 DOI: https://doi.org/10.1096/fasebj.2020.34.s1.00116

Sies H., Berndt C., Jones D. P. Oxidative stress. Annual Review of Biochemistry. 2017; 86:715–748.

https://doi.org/10.1146/annurev-biochem-061516-045037 DOI: https://doi.org/10.1146/annurev-biochem-061516-045037

Sari Y. Chronic inhalation of pod-based e-cigarette aerosols on inflammatory biomarkers in the central nervous and peripheral systems. Jordan Journal of Pharmaceutical Sciences. 2023; 16(2):443. https://doi.org/10.35516/jjps.v16i2.1482 DOI: https://doi.org/10.35516/jjps.v16i2.1482

Hajjo R., Sabbah D. A., Al Bawab A. Q. Unlocking the potential of the human microbiome for identifying disease diagnostic biomarkers. Diagnostics. 2022; 12(7):1742.

https://doi.org/10.3390/diagnostics12071742 DOI: https://doi.org/10.3390/diagnostics12071742

Galiè M., Costanzo M., Nodari A., Boschi F., Calderan L., Mannucci S., Covi V., Tabaracci G., Malatesta M. Mild ozonisation activates antioxidant cell response by the Keap1/Nrf2 dependent pathway. Free Radical Biology & Medicine. 2018; 124:114–121. https://doi.org/10.1016/j.freeradbiomed.2018.05.093 DOI: https://doi.org/10.1016/j.freeradbiomed.2018.05.093

Fernández-Checa J. C., Kaplowitz N., García-Ruiz C., Colell A., Miranda M., Marí M., Ardite E., Morales A. GSH transport in mitochondria: defense against TNF-induced oxidative stress and alcohol-induced defect. The American Journal of Physiology. 1997; 273(1 Pt 1):G7–G17. https://doi.org/10.1152/ajpgi.1997.273.1.G7 DOI: https://doi.org/10.1152/ajpgi.1997.273.1.G7

Rose S., Melnyk S., Pavliv O., Bai S., Nick T. G., Frye R. E., James S. J. Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Translational Psychiatry. 2012; 2(7):e134. https://doi.org/10.1038/tp.2012.61 DOI: https://doi.org/10.1038/tp.2012.61

Rossignol D. A., Frye R. E. Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism. Frontiers in Physiology. 2014; 5:150.

https://doi.org/10.3389/fphys.2014.00150 DOI: https://doi.org/10.3389/fphys.2014.00150

Hajjo R., Sabbah D. A., Abusara O. H., Al Bawab A. Q. A review of the recent advances in Alzheimer’s disease research and the utilization of network biology approaches for prioritizing diagnostics and therapeutics. Diagnostics. 2022; 12(12):2975.

https://doi.org/10.3390/diagnostics12122975 DOI: https://doi.org/10.3390/diagnostics12122975

López-Hurtado E., Prieto J. J. A microscopic study of language-related cortex in autism. American Journal of Biochemistry and Biotechnology. 2008; 4(2):130–145. https://doi.org/10.3844/ajbbsp.2008.130.145 DOI: https://doi.org/10.3844/ajbbsp.2008.130.145

Chauhan A., Chauhan V. Oxidative stress in autism. Pathophysiology: The Official Journal of the International Society for Pathophysiology. 2006; 13(3):171–181. https://doi.org/10.1016/J.PATHOPHYS.2006.05.007 DOI: https://doi.org/10.1016/j.pathophys.2006.05.007

Lord C., Elsabbagh M., Baird G., Veenstra-Vanderweele J. Autism spectrum disorder. Lancet (London, England). 2018; 392(10146):508–520. https://doi.org/10.1016/S0140-6736(18)31129-2 DOI: https://doi.org/10.1016/S0140-6736(18)31129-2

Murphy C. M., Wilson C. E., Robertson D. M., Ecker C., Daly E. M., Hammond N., Galanopoulos A., Dud I., Murphy D. G., McAlonan G. M. Autism spectrum disorder in adults: diagnosis, management, and health services development. Neuropsychiatric Disease and Treatment. 2016; 12:1669–1686.

https://doi.org/10.2147/NDT.S65455 DOI: https://doi.org/10.2147/NDT.S65455

Liu X., Lin J., Zhang H., Khan N. U., Zhang J., Tang X., Cao X., Shen L. Oxidative stress in autism spectrum disorder—current progress of mechanisms and biomarkers. Frontiers in Psychiatry. 2022; 13:813304. https://doi.org/10.3389/fpsyt.2022.813304/bibtex

Chen L., Shi X. J., Liu H., Mao X., Gui L. N., Wang H., Cheng Y. Oxidative stress marker aberrations in children with autism spectrum disorder: a systematic review and meta-analysis of 87 studies (N = 9109). Translational Psychiatry. 2021; 11(1):1–10. https://doi.org/10.1038/s41398-020-01135-3 DOI: https://doi.org/10.1038/s41398-020-01135-3

Ghezzo A., Visconti P., Abruzzo P. M., Bolotta A., Ferreri C., Gobbi G., Malisardi G., Manfredini S., Marini M., Nanetti L., Pipitone E., Raffaelli F., Resca F., Vignini A., Mazzanti L. Oxidative stress and erythrocyte membrane alterations in children with autism: correlation with clinical features. PLOS ONE. 2013; 8(6):e66418.

https://doi.org/10.1371/journal.pone.0066418 DOI: https://doi.org/10.1371/journal.pone.0066418

Efe A., Neşelioğlu S., Soykan A. An investigation of the dynamic thiol/disulfide homeostasis, as a novel oxidative stress plasma biomarker, in children with autism spectrum disorders. Autism Research. 2021; 14(3):473–487. https://doi.org/10.1002/aur.2436 DOI: https://doi.org/10.1002/aur.2436

Werling D. M., Geschwind D. H. Sex differences in autism spectrum disorders. Current Opinion in Neurology. 2013; 26(2):146–153. https://doi.org/10.1097/WCO.0b013e32835ee548 DOI: https://doi.org/10.1097/WCO.0b013e32835ee548

Jacquemont S., Coe B. P., Hersch M., Duyzend M. H., Krumm N., Bergmann S., Beckmann J. S., Rosenfeld J. A., Eichler E. E. A higher mutational burden in females supports a “female protective model” in neurodevelopmental disorders. American Journal of Human Genetics. 2014; 94(3):415–425. https://doi.org/10.1016/j.ajhg.2014.02.001 DOI: https://doi.org/10.1016/j.ajhg.2014.02.001

Ostatníková D., Lakatošová S., Babková J., Hodosy J., Celec P. Testosterone and the brain: from cognition to autism. Physiological Research. 2020; 69(Suppl 3):S403–S419. https://doi.org/10.33549/physiolres.934592 DOI: https://doi.org/10.33549/10.33549/physiolres.934592

Xie S., Karlsson H., Dalman C., Widman L., Rai D., Gardner R. M., Magnusson C., Sandin S., Tabb L. P., Newschaffer C. J., Lee B. K. The familial risk of autism spectrum disorder with and without intellectual disability. Autism Research: Official Journal of the International Society for Autism Research. 2020; 13(12):2242–2250. https://doi.org/10.1002/aur.2417 DOI: https://doi.org/10.1002/aur.2417

Sandin S., Lichtenstein P., Kuja-Halkola R., Larsson H., Hultman C. M., Reichenberg A. The familial risk of autism. JAMA. 2014; 311(17):1770–1777. https://doi.org/10.1001/jama.2014.4144 DOI: https://doi.org/10.1001/jama.2014.4144

Satterstrom F. K., Kosmicki J. A., Wang J., Breen M. S., De Rubeis S., An J.-Y., Peng M., Collins R., Grove J., Klei L., Stevens C., Reichert J., Mulhern M. S., Artomov M., Gerges S., Sheppard B., Xu X., Bhaduri A., Norman U., … Buxbaum J. D. Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism. Cell. 2020; 180(3):568–584.e23.

https://doi.org/10.1016/j.cell.2019.12.036 DOI: https://doi.org/10.1016/j.cell.2019.12.036

Genovese A., Butler M. G. The autism spectrum: behavioral, psychiatric and genetic associations. Genes. 2023; 14(3). https://doi.org/10.3390/genes14030677 DOI: https://doi.org/10.3390/genes14030677

Choi L., An J.-Y. Genetic architecture of autism spectrum disorder: lessons from large-scale genomic studies. Neuroscience & Biobehavioral Reviews. 2021; 128:244–257. https://doi.org/10.1016/j.neubiorev.2021.06.028 DOI: https://doi.org/10.1016/j.neubiorev.2021.06.028

Lai M.-C., Lombardo M. V., Baron-Cohen S. Autism. Lancet (London, England). 2014; 383(9920):896–910. https://doi.org/10.1016/S0140-6736(13)61539-1 DOI: https://doi.org/10.1016/S0140-6736(13)61539-1

White S. W., Oswald D., Ollendick T., Scahill L. Anxiety in children and adolescents with autism spectrum disorders. Clinical Psychology Review. 2009; 29(3):216–229. https://doi.org/10.1016/j.cpr.2009.01.003 DOI: https://doi.org/10.1016/j.cpr.2009.01.003

Tuchman R., Rapin I. Epilepsy in autism. The Lancet Neurology. 2002; 1(6):352–358.

https://doi.org/10.1016/s1474-4422(02)00160-6 DOI: https://doi.org/10.1016/S1474-4422(02)00160-6

Liu X., Lin J., Zhang H., Khan N. U., Zhang J., Tang X., Cao X., Shen L. Oxidative stress in autism spectrum disorder—current progress of mechanisms and biomarkers. Frontiers in Psychiatry. 2022; 13:813304. https://doi.org/10.3389/fpsyt.2022.813304 DOI: https://doi.org/10.3389/fpsyt.2022.813304

Ayala A., Muñoz M. F., Argüelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxidative Medicine and Cellular Longevity. 2014; 2014:360438.

https://doi.org/10.1155/2014/360438 DOI: https://doi.org/10.1155/2014/360438

Frustaci A., Neri M., Cesario A., Adams J., Domenici E., Dalla Bernardina B., Bonassi S. Oxidative stress-related biomarkers in autism: systematic review and meta-analyses. Free Radical Biology & Medicine. 2012; 52:2128–2141. https://doi.org/10.1016/j.freeradbiomed.2012.03.011 DOI: https://doi.org/10.1016/j.freeradbiomed.2012.03.011

Nasrallah O., Alzeer S. Measuring some oxidative stress biomarkers in autistic Syrian children and their siblings: a case-control study. Biomarker Insights. 2022; 17:11772719221123912. https://doi.org/10.1177/11772719221123913 DOI: https://doi.org/10.1177/11772719221123913

Meguid N. A., Dardir A. A., Abdel-Raouf E. R., Hashish A. Evaluation of oxidative stress in autism: defective antioxidant enzymes and increased lipid peroxidation. Biological Trace Element Research. 2011; 143(1):58–65. https://doi.org/10.1007/s12011-010-8840-9 DOI: https://doi.org/10.1007/s12011-010-8840-9

Bjørklund G., Meguid N. A., El-Bana M. A., Tinkov A. A., Saad K., Dadar M., Hemimi M., Skalny A. V., Hosnedlová B., Kizek R., Osredkar J., Urbina M. A., Fabjan T., El-Houfey A. A., Kałużna-Czaplińska J., Gątarek P., Chirumbolo S. Oxidative stress in autism spectrum disorder. Molecular Neurobiology. 2020; 57(5):2314–2332. https://doi.org/10.1007/s12035-019-01742-2 DOI: https://doi.org/10.1007/s12035-019-01742-2

Usui N., Kobayashi H., Shimada S. Neuroinflammation and oxidative stress in the pathogenesis of autism spectrum disorder. International Journal of Molecular Sciences. 2023; 24(6).

https://doi.org/10.3390/ijms24065487 DOI: https://doi.org/10.3390/ijms24065487

Ahadullah, Yau S., Lu H., Lee T. M. C., Guo H., Chan C. C. H. PM2.5 as a potential risk factor for autism spectrum disorder: its possible link to neuroinflammation, oxidative stress and changes in gene expression. Neuroscience & Biobehavioral Reviews. 2021; 128:534–548. https://doi.org/10.1016/j.neubiorev.2021.06.043 DOI: https://doi.org/10.1016/j.neubiorev.2021.06.043

Baig S., Parvaresh Rizi E., Chia C., Shabeer M., Aung N., Loh T. P., Magkos F., Vidal-Puig A., Seet R. C. S., Khoo C. M., Toh S.-A. Genes involved in oxidative stress pathways are differentially expressed in circulating mononuclear cells derived from obese insulin-resistant and lean insulin-sensitive individuals following a single mixed-meal challenge. Frontiers in Endocrinology. 2019; 10. DOI: https://doi.org/10.3389/fendo.2019.00256

Morimoto M., Hashimoto T., Tsuda Y., Nakatsu T., Kitaoka T., Kyotani S. Assessment of oxidative stress in autism spectrum disorder using reactive oxygen metabolites and biological antioxidant potential. PLOS ONE. 2020; 15(5):e0233550. https://doi.org/10.1371/JOURNAL.PONE.0233550 DOI: https://doi.org/10.1371/journal.pone.0233550

Membrino V., Paolo A. Di, Alia S., Papiri G., Vignini A. The role of oxidative stress in autism spectrum disorder: a narrative literature review. Oxygen. 2023; 3(1):34–44. https://doi.org/10.3390/OXYGEN3010004 DOI: https://doi.org/10.3390/oxygen3010004

Hu T., Dong Y., He C., Zhao M., He Q. The gut microbiota and oxidative stress in autism spectrum disorders (ASD). Oxidative Medicine and Cellular Longevity. 2020; 2020:8396708. https://doi.org/10.1155/2020/8396708 DOI: https://doi.org/10.1155/2020/8396708

Downloads

Published

2025-09-24

How to Cite

Al-Ramahi, A., Zakaraya, Z., AlTamimi, L., Hailat, M., Hamad, M. F., Abu Dayyih, W., Alabbadi, I., AlRaoush, Y., Al-Omari, L., Ahmed, K. A.-A., & Alhusban, A. A. (2025). Impact of Oxidative Stress on Jordanian Children with Autism Spectrum Disorder. Jordan Journal of Pharmaceutical Sciences, 18(3), 878–890. https://doi.org/10.35516/jjps.v18i3.2625

Issue

Section

Articles

Most read articles by the same author(s)