Migren Hastalığının Patogenezinde Oksidatif Stres, Damar Fizyopatolojisini Etkileyen Faktörler ve Enflamasyonun Rolü

Year 2021, Volume: 18 Issue: 1, 75 - 81, 28.04.2021

Eray Metin Güler , Ülker Anadol Hayriye Polat Ahmet Kılınç Destina Yalçın , A. Suha Yalçın

https://doi.org/10.35440/hutfd.883824

Abstract

Amaç: Çalışmamızda migren tanısı konmuş hastalar ile sağlıklı kontrol grubu arasında oksidatif stres, damar fizyopatolojisi ve enflamasyon biyobelirteçleri açısından bir fark olup olmadığının araştırılması amaçlandı.
Materyal ve Metod: SBÜ Ümraniye Eğitim Araştırma Hastanesi Nöroloji Polikliniğine başvuran, 18 - 49 yaş arasında olup migren tanı kriterlerine uyan ve sistemik herhangi bir hastalığı olmayan 27 hasta ile 27 sağlıklı kişiden kan ve idrar örnekleri alındı. İdrarda malondialdehit, eritrositlerde glutatyon, glutatyonla ilgili enzimler, süperoksit dismutaz, katalaz, malondialdehit ve protein karbonilleri, plazmada malondialdehit, bilirubin, ürik asit ve albümin gibi oksidatif stres biyobelirteçlerine, damar fizyopatolojisi biyobelirteçlerinden trombosit ve fibrinojene, enflamasyon biyobelirteçlerinden ise interkökin (IL) 1β, IL6, IL10, tümör nekrozis faktör (TNF) α, c reaktif protein (CRP) ve ferritin düzeyleri ölçüldü.
Bulgular: Hasta grubunda glutatyon ve glutatyonla ilgili enzimlerin yanında süperoksit dismutaz ve katalaz değerleri kontrol grubuna kıyasla istatistiksel olarak anlamlı düşük (p<0,001) bulundu. Plazma albümin düzeylerinde gruplar arasında istatistiksel fark görülmedi. Ürik asit ve total bilirubin düzeylerinde ise hasta grubundaki düzeyler istatistiksel olarak anlamlı yüksek (p<0,001) bulundu. Benzer şekilde oksidatif hasar belirteçleri olan protein karbonilleri ile plazma, eritrosit ve idrar malondialdehit düzeyleri hasta grubunda istatistiksel olarak anlamlı yüksek (p<0,001) bulundu. Damar fizyopatolojisi belirteçlerinden trombosit sayısı ve fibrinojen düzeylerinin hasta grubunda anlamlı olarak arttığı (p<0,001) gözlendi. Enflamasyon belirteçlerinden IL1β, IL6, IL10 ve TNFα düzeyleri hasta grubunda istatistiksel olarak anlamlı yüksek (p<0,001) bulunurken, CRP ve ferritin düzeyleri düşüktü.
Sonuç: Migren hastalarında oksidatif stres, damar fizyopatolojisi ve enflamasyon belirteçleri birlikte değerlendirildiğinde, hastalardaki baskılanan ve azalan antioksidan düzeylerinin oksidatif stresi arttırdığı dolayısıyla enflamasyon ve damar fizyopatolojisi değişikliklerine neden olduğu sonucuna varıldı.

Keywords

damar fizyopatolojisi, enflamasyon, migren, oksidatif stres

Supporting Institution

Marmara Üniversitesi Bilimsel Araştırma Projeleri Birimi

Project Number

SAG-C-YLP-110412-0070

Thanks

Makalemiz Eray Metin Güler’in yüksek lisans tezinden üretilmiştir. Ayrıca, 6-11 Temmuz 2013 tarihinde gerçekleşen Federation of European Biochemical Societies Congress toplantısında “The Role of Oxidative / Antioxidative Balance, Vascular Pathophysiology and Inflammation in Migraine” başlıklı poster olarak sunulmuştur.

Role of oxidative stress, factors affecting vascular physiopathology and inflammation in the pathogenesis of migraine disease

Abstract

Background: We compared oxidative stress, vascular pathophysiology, and inflammation markers of migraine patients with healthy volunteers.
Material and Method: Blood and urine samples were obtained from 27 healthy individuals and 27 patients with a diagnosis of migraine who applied to Neurology Outpatient Clinics of Umraniye Research and Training Hospital. Participants were aged between 18 – 49 years. Patients had their diagnosis established prior to the study, and the volunteers in the control group had no systemic disease or relevant disorders. Urine samples were tested for malondialdehyde while erythrocytes were investigated for glutathione, glutathione related enzymes, superoxide dismutase, catalase, malondialdehyde, and protein carbonyls. Plasma samples were analyzed for malondialdehyde, bilirubin, uric acid, and albumin as oxidative stress parameters. Thrombocyte count and fibrinogen levels were measured for vascular physiopathology, and IL1β, IL6, IL10, TNFα, CRP, and ferritin were used as inflammation markers.
Results: In addition to glutathione and glutathione-related enzymes, superoxide dismutase and catalase values were found to be statistically significantly lower (p<0.001) in the patient group. Albumin levels were similar in both groups, whereas uric acid and bilirubin levels were significantly higher (p<0.001) in the patient group. Similarly, protein carbonyls, which are oxidative damage markers, as well as urine, plasma, and erythrocyte malondialdehyde levels were significantly higher (p<0.001) in the patient group. Thrombocyte count and fibrinogen levels, both of which are vascular physiopathology markers, were found to increase in the patient group (p<0.001). The participants in the patient group had significantly higher (p<0.001) levels of IL1β, IL6, IL10, and TNFα as inflammation markers, on the other hand, CRP and ferritin levels were lower.
Conclusion: Considering oxidative stress, vascular physiopathology, and inflammation markers as a whole, we suggest that patients with migraine had increased oxidative stress due to suppressed and decreased levels of antioxidants and consequently had inflammatory and vascular changes.

Keywords

Vascular Physiopathology, Inflammation, Migraine, Oxidative stress

Project Number

SAG-C-YLP-110412-0070

References

• 1. Bulboacă AE, Stănescu IC, Bolboacă SD, Bulboacă AC, Bodizs GI, Nicula CA. Retinal Nerve Fiber Layer Thickness and Oxidative Stress Parameters in Migraine Patients without Aura: A Pilot Study. Antioxidants. 2020;9(6):494.
• 2. Saylor D, Steiner TJ, editors. The global burden of headache. Seminars in neurology; 2018: Thieme Medical Publishers.
• 3. Edvinsson L, Haanes KA, Warfvinge K. Does inflammation have a role in migraine? Nature Reviews Neurology. 2019;15(8):483-90.
• 4. Cesarone MR, Dugall M, Hu S, Belcaro G, Hosoi M, Scipione V, et al. Episodic primary migraine headache: supplementary prophylaxis with Pycnogenol® prevents attacks and controls oxidative stress. Panminerva medica. 2020;62(2):102-8.
• 5. Othmène YB, Hamdi H, Salem IB, Annabi E, Amara I, Neffati F, et al. Oxidative stress, DNA damage and apoptosis induced by tebuconazole in the kidney of male Wistar rat. Chemico-Biological Interactions. 2020;330:109114.
• 6. Vasques MAA, Fonseca EdBM. A review on migraine and oxidative stress. Revista de Medicina e Saúde de Brasília. 2020;9(2).
• 7. Neri M, Frustaci A, Milic M, Valdiglesias V, Fini M, Bonassi S, et al. A meta-analysis of biomarkers related to oxidative stress and nitric oxide pathway in migraine. Cephalalgia. 2015;35(10):931-7.
• 8. Danese E, Montagnana M, Lippi G. Platelets and migraine. Thrombosis research. 2014;134(1):17-22.
• 9. Lukacs M, Tajti J, Fulop F, Toldi J, Edvinsson L, Vecsei L. Migraine, neurogenic inflammation, drug development-pharmacochemical aspects. Current medicinal chemistry. 2017;24(33):3649-65.
• 10. Beutler E. Red cell metabolism. A manual of biochemical methods. 1975:11-2.
• 11. Mannervik B, Guthenberg C. [28] Glutathione transferase (human placenta). Methods in enzymology. 77: Elsevier; 1981. p. 231-5.
• 12. Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases: the first enzymatic step in mercapturic acid formation. Journal of biological Chemistry. 1974;249(22):7130-9.
• 13. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clinical chemistry. 1988;34(3):497-500.
• 14. Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz A-G, et al. [49] Determination of carbonyl content in oxidatively modified proteins. Methods in enzymology. 1990;186:464-78.
• 15. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical biochemistry. 1979;95(2):351-8.
• 16. Zhou H, Kato A, Miyaji T, Yasuda H, Fujigaki Y, Yamamoto T, et al. Urinary marker for oxidative stress in kidneys in cisplatin-induced acute renal failure in rats. Nephrology Dialysis Transplantation. 2006;21(3):616-23.
• 17. Guler EM, Gokce M, Bacaksiz A, Kocyigit A. Urotensin-II, oxidative stress, and inflammation increase in hypertensive and resistant hypertensive patients. Clinical and Experimental Hypertension. 2020:1-6.
• 18. Burch RC, Buse DC, Lipton RB. Migraine: epidemiology, burden, and comorbidity. Neurologic clinics. 2019;37(4):631-49.
• 19. Halliwell B, Gutteridge JM. Free radicals in biology and medicine: Oxford University Press, USA; 2015.
• 20. Abdel-Salam OM, Salem NA, Hussein JS. Effect of aspartame on oxidative stress and monoamine neurotransmitter levels in lipopolysaccharide-treated mice. Neurotoxicity research. 2012;21(3):245-55.
• 21. Bockowski L, Sobaniec W, Kulak W, Smigielska-Kuzia J, Bockowski L, Sobaniec W, et al. Serum and intraerythrocyte antioxidant enzymes and lipid peroxides in children with migraine. Pharmacological reports. 2008;60(4):542.
• 22. Tripathi GM, Kalita J, Misra UK. A study of oxidative stress in migraine with special reference to prophylactic therapy. International Journal of Neuroscience. 2018;128(4):318-24.
• 23. Aytaç B, Coşkun Ö, Alioğlu B, Durak ZE, Büber S, Tapçi E, et al. Decreased antioxidant status in migraine patients with brain white matter hyperintensities. Neurological Sciences. 2014;35(12):1925-9.
• 24. Bolayir E, Celik K, Kugu N, Yilmaz A, Topaktas S, Bakir S. Intraerythrocyte antioxidant enzyme activities in migraine and tension-type headaches. JOURNAL-CHINESE MEDICAL ASSOCIATION. 2004;67(6):263-7.
• 25. Powers SK, Radak Z, Ji LL. Exercise‐induced oxidative stress: past, present and future. The Journal of physiology. 2016;594(18):5081-92.
• 26. Arngrim N, Schytz HW, Britze J, Amin FM, Vestergaard MB, Hougaard A, et al. Migraine induced by hypoxia: an MRI spectroscopy and angiography study. Brain. 2016;139(3):723-37.
• 27. Williamson DJ, Hargreaves RJ. Neurogenic inflammation in the context of migraine. Microscopy research and technique. 2001;53(3):167-78.
• 28. Noseda R, Burstein R. Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain. PAIN®. 2013;154:S44-S53.
• 29. Stam AH, Weller CM, Janssens ACJ, Aulchenko YS, Oostra BA, Frants RR, et al. Migraine is not associated with enhanced atherosclerosis. Cephalalgia. 2013;33(4):228-35.
• 30. Schürks M, Rist PM, Bigal ME, Buring JE, Lipton RB, Kurth T. Migraine and cardiovascular disease: systematic review and meta-analysis. Bmj. 2009;339.
• 31. Tietjen GE, Collins SA. Hypercoagulability and migraine. Headache: The Journal of Head and Face Pain. 2018;58(1):173-83.
• 32. Jha S, Varma M, Garg R, Kar A. Platelet aggregation in migraine. The Journal of the Association of Physicians of India. 1992;40(3):153-4.
• 33. D'andrea G, Cananzi A, Perini F, Alecci M, Zamberlan F, Hasselmark L, et al. Decreased collagen-induced platelet aggregation and increased platelet arginine levels in migraine: a possible link with the NO pathway. Cephalalgia. 1994;14(5):352-6.
• 34. Tepper NK, Whiteman MK, Zapata LB, Marchbanks PA, Curtis KM. Safety of hormonal contraceptives among women with migraine: a systematic review. Contraception. 2016;94(6):630-40.
• 35. von Känel R, Mills PJ, Fainman C, Dimsdale JE. Effects of psychological stress and psychiatric disorders on blood coagulation and fibrinolysis: a biobehavioral pathway to coronary artery disease? Psychosomatic medicine. 2001;63(4):531-44.
• 36. Dong T, Cheng Y-W, Yang F, Sun P-W, Zhu C-J, Zhu L, et al. Chronic stress facilitates the development of deep venous thrombosis. Oxidative medicine and cellular longevity. 2015;2015.
• 37. Kurth T, Ridker P, Buring J. Migraine and biomarkers of cardiovascular disease in women. Cephalalgia. 2008;28(1):49-56.
• 38. Tietjen GE, Khubchandani J, Herial N, Palm-Meinders IH, Koppen H, Terwindt GM, et al. Migraine and vascular disease biomarkers: a population-based case-control study. Cephalalgia. 2018;38(3):511-8.
• 39. Peroutka SJ. Neurogenic inflammation and migraine: implications for the therapeutics. Molecular interventions. 2005;5(5):304.
• 40. Diener H. RPR100893, a substance-P antagonist, is not effective in the treatment of migraine attacks. Cephalalgia. 2003;23(3):183-5.
• 41. Perini F, D'Andrea G, Galloni E, Pignatelli F, Billo G, Alba S, et al. Plasma cytokine levels in migraineurs and controls. Headache: The Journal of Head and Face Pain. 2005;45(7):926-31.
• 42. Fidan I, Yüksel S, Ýmir T, İrkeç C, Aksakal FN. The importance of cytokines, chemokines and nitric oxide in pathophysiology of migraine. Journal of neuroimmunology. 2006;171(1-2):184-8.
• 43. Johnson KW, Bolay H. Neurogenic inflammatory mechanisms: Lippincott, Williams & Wilkins, PA, USA; 2006.
• 44. Tanure MTA, Gomez RS, Hurtado RCL, Teixeira AL, Domingues RB. Increased serum levels of brain-derived neurotropic factor during migraine attacks: a pilot study. J Headache Pain. 2010;11(5):427-30.
• 45. Yücel M, Kotan D, Gurol Çiftçi G, Çiftçi I, Cikriklar H. Serum levels of endocan, claudin-5 and cytokines in migraine. Eur Rev Med Pharmacol Sci. 2016;20(5):930-6.
• 46. Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. Pathophysiology of migraine: a disorder of sensory processing. Physiological reviews. 2017.