تأثير الإجهاد التأكسدي على الأطفال الأردنيين المصابين باضطراب طيف التوحد
DOI:
https://doi.org/10.35516/jjps.v18i3.2625الكلمات المفتاحية:
اضطراب طيف التوحد، أطفال أردنيون، غلوتاثيون بيروكسيداز، سوبر أكسيد ديسميوتاز، مالونديالدهيد، اضطراب نقص الانتباه مع فرط النشاط ((ADHD، القلق، الصرع، الإجهاد التأكسديالملخص
الخلفية: اضطراب طيف التوحد (ASD) هو اضطراب نمائي عصبي لا تزال مسبباته غير معروفة ولا توجد له مؤشرات حيوية سريرية. وقد أبرزت دراسات حديثة الدور المحتمل للإجهاد التأكسدي والتغيرات الأيضية في اضطراب طيف التوحد. إلا أنه لا يُعرف الكثير عن هذه التغيرات لدى المصابين باضطراب طيف التوحد في الأردن.
الأهداف: هدفت هذه الدراسة إلى تقييم الواسمات الحيوية للإجهاد التأكسدي لدى الأطفال الأردنيين المصابين باضطراب طيف التوحد، والتحقيق في الارتباطات المحتملة لهذه الواسمات بالسمات السريرية للاضطراب.
المنهجية: شملت هذه الدراسة المقطعية 80 طفلًا أردنيًا قُسّموا إلى مجموعتين: مجموعة المرضى (شُخِّص أفرادها باضطراب طيف التوحد، وعددهم 40) والمجموعة الضابطة (من الأصحاء، وعددهم 40). تم استقصاء توزيع اضطراب طيف التوحد بين المشاركين وتقييم مدى انتشار الحالات المرضية المصاحبة. كما تم تقييم الواسمات الحيوية للإجهاد التأكسدي، بما في ذلك إنزيم غلوتاثيون بيروكسيداز (GPX)، وإنزيم سوبر أكسيد ديسميوتاز (SOD)، ومالونديالدهيد (MDA).
النتائج: كان اضطراب طيف التوحد أكثر شيوعًا بين الذكور (65% في مجموعة المرضى) وبين الأشخاص الذين لديهم تاريخ عائلي للإصابة بالاضطراب (55%). كما تضمنت الحالات المرضية المصاحبة الشائعة كلاً من اضطراب نقص الانتباه مع فرط النشاط (ADHD) بنسبة 42.5%، والقلق بنسبة 25%، والصرع بنسبة 15%. كانت مستويات إنزيم GPX لدى الأطفال المصابين بالتوحد أقل بشكل ملحوظ (2.72 ± 0.9 بيكومول/مل مقابل 7.74 ± 2.5 بيكومول/مل في المجموعة الضابطة، p<0.005)، وكذلك مستويات إنزيم SOD (1.74 ± 0.75 نانوغرام/مل مقابل 2.93 ± 0.98 نانوغرام/مل في المجموعة الضابطة، p<0.005)، في حين كانت مستويات MDA لديهم أعلى (16 ± 1.95 نانومول/مل مقابل 5.46 ± 1.57 نانومول/مل في المجموعة الضابطة، p<0.005).
الخلاصة: تشير هذه الدراسة إلى وجود ارتباط محتمل بين اضطراب طيف التوحد والإجهاد التأكسدي. وعلى الرغم من ضرورة إجراء المزيد من البحوث، فإن هذه النتائج تسهم في تعزيز فهمنا لإمراضية اضطراب طيف التوحد وقد توجه الأساليب التشخيصية والعلاجية المستقبلية. كما تشير معاملات ارتباط بيرسون إلى أن زيادة الإجهاد التأكسدي، المتمثلة في انخفاض مستويات إنزيمي GPX وSOD وارتفاع مستوى MDA، قد تكون مرتبطة بظهور السمات السريرية وشدتها لدى المصابين باضطراب طيف التوحد.
المراجع
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







