The Effect of Topiramate on Ischemia-Modified Albumin and Prolidase Enzyme Levels in Nitroglycerin-Induced Adolescent Rat Brain Tissue

Yıl 2023, Cilt: 11 Sayı: 3, 153 - 157, 15.10.2023

Yılmaz Koçak , Nesrin Ceylan , Maşallah Ermaya , Halit Demir , Yıldıray Basbugan

Öz

Aim: Migraine is a neurological disorder accompanied by episodic headaches that can also occur in children and adolescents. Environmental and genetic factors play a role in the pathogenesis of migraine and the possible contribution of oxidative stress (OS) is debated. Therefore, the present study focused on the possible effect of topiramate (TPM) on the oxidative stress markers ischemia-modified albumin (IMA) and prolidase enzyme activity in nitroglycerin (NTG)-induced brain tissue of adolescent rats.
Material and Method: In this study, 32 male Wistar albino rats aged 6 weeks (adolescence) were used. Rats were divided into four groups with 8 animals in each group. Rats were administered NTG intraperitoneally (i.p.) once daily and topiramate (TPM) orally (p.o.) twice daily. Groups and doses were formed as follows. Group 1: Control group; Group 2: NTG (10 mg/kg) group, Group 3: NTG (10 mg/kg) + TPM (50 mg/kg) group and Group 4: Only TPM (50 mg/kg) group. Animals were sacrificed at the end of the experiment. After the brain tissues were homogenized, IMA and prolidase enzyme activities were measured spectrophotometrically.
Result: IMA and prolidase levels increased in the NTG-treated group and this increase was found to be significant when compared with the control group (p≤0.05). The combination of NTG+TPM brought IMA and prolidase levels closer to the control group and numerically reduced them compared to the NTG group. Only the TPM group showed a significant decrease compared to the NTG group (p≤0.05). In addition, IMA and prolidase levels of TPM were close to the control group.
Conclusion: NTG increased IMA and prolidase levels, indicating that it may trigger oxidative stress. TPM partially reversed IMA and prolidase levels. These results may support the hypothesis that TPM may have an antioxidant effect that suppresses OS. Understanding the pharmacodynamic effects of TPM may enable its more effective use as a therapeutic agent.

Anahtar Kelimeler

Topiramate, Nitroglycerin, IMA, Prolidase, Adolescent rat, Oxidative stress

Destekleyen Kurum

None

Proje Numarası

None

Topiramatın Nitrogliserinle İndüklenen Adolesan Sıçanların Beyin Dokusunda İskemi Modifiye Albümin ve Prolidaz Enzim Düzeyleri Üzerine Etkisi

Öz

Amaç: Migren, çocuklarda ve ergenlerde görülebilen epizodik baş ağrısının eşlik ettiği nörolojik bir bozukluktur. Migrenin patogenezinde çevresel ve genetik faktörler rol oynar ve oksidatif stresin (OS) olası katkısı tartışılmaktadır. Bu yüzden sunulan çalışma, nitrogliserin (NTG) ile indüklenen adolesan ratların beyin dokusunda, topiramat’ın (TPM) oksidatif stres belirteçleri olan iskemi modifiye albümin (IMA) ve prolidaz enzim aktivitesi üzerine olası etkisine odaklanmıştır.
Gereç ve Yöntem: Bu çalışmada, Wistar albino ırkı 6 haftalık (adolesan dönem) 32 adet erkek rat kullanıldı. Sıçanlar, her grupta 8 hayvan olacak şekilde dört gruba ayrıldı. Sıçanlara, NTG intraperitoneal (i.p.) günde 1 kez ve topiramat (TPM) oral (p.o.) günde 2 kez olarak uygulandı. Gruplar ve dozlar aşağıdaki gibi oluşturuldu. Group 1: kontrol grubu; Group 2: NTG (10mg/kg) grubu, Group 3: NTG (10 mg/kg) + TPM (50 mg/kg) grubu ve Group 4: Sadece TPM (50 mg/kg) grubu. Hayvanlar deneyin sonunda sakrifiye edildi. Elde edilen beyin dokuları homojenize edildikten sonra, IMA ve prolidaz enzim aktiviteleri spektrofotometrik ölçüldü.
Bulgular: NTG ile tedavi edilen grupta IMA ve prolidaz seviyelerinde artış görülmüş ve bu artış kontrol grubuyla karşılaştırıldığında anlamlı bulunmuştur (p≤0,05). NTG+TPM kombinasyonu, IMA ve prolidaz seviyelerini kontrol grubuna yaklaştırmış ve NTG grubuna kıyasla sayısal olarak azaltmıştır. Sadece TPM uygulanan grup, NTG grubuna göre anlamlı azalış sergiledi (p≤0.05). Ayrıca, TPM'nin IMA ve prolidaz düzeyleri kontrol grubuna göre' yakın değerler aldı.
Sonuç: NTG, IMA ve prolidaz seviyelerini artırarak OS’u tetikleyebileceğini göstermiştir. TPM ise kısmende olsa IMA ve prolidaz düzeylerini tersine çevirdi. Bu sonuçlar, TPM’nin OS’u baskılayan antioksidan etkiye sahip olabileceği varsayımını destekleyebilir. TPM'nin farmakodinamik etkilerinin anlaşılması, terapötik bir ajan olarak daha etkili bir şekilde kullanılmasını sağlayabilir.

Anahtar Kelimeler

Topiramat, Nitrogliserin, IMA, Prolidaz, Adolesan rat, Oksidatif stres

Proje Numarası

None

Kaynakça

• 1. Gibler RC, Peugh JL, Coffey CS, et al. Impact of preventive pill-based treatment on migraine days: A secondary outcome study of the Childhood and Adolescent Migraine Prevention (CHAMP) trial and a comparison of self-report to nosology-derived assessments. Headache J Head Face Pain. 2023;63(6):805–12.
• 2. Li R, Liu Y, Chen N, Zhang Y, Song G, et al. Valproate Attenuates Nitroglycerin-Induced Trigeminovascular Activation by Preserving Mitochondrial Function in a Rat Model of Migraine. Med Sci Monit. 2016;22: 3229–3237.
• 3. Lateef T, Witonsky K, He J, Ries Merikangas K. Headaches and sleep problems in US adolescents: Findings from the National Comorbidity Survey – Adolescent Supplement (NCS-A). Cephalalgia. 2019;39(10):1226–35
• 4. Sufka KJ, Staszko SM, Johnson AP, Davis ME, Davis RE, et al. Clinically relevant behavioral endpoints in a recurrent nitroglycerin migraine model in rats. J Headache Pain. 2016;17(1):1–7.
• 5. Carol, Corsetti G, Pasini E, Dioguardi FS, Sahni G, Narula J, et al. Spasmogenic Effects of the Proteasome Inhibitor Carfilzomib on Coronary Resistance, Vascular Tone and Reactivity. EBioMedicine. 2017;21:206–12.
• 6. Demartini C, Greco R, Zanaboni AM, Sances G, De Icco R, et al. Nitroglycerin as a comparative experimental model of migraine pain: From animal to human and back. Prog Neurobiol. 2019;177:15–32.
• 7. Neri M, Frustaci A, Milic M, Valdiglesias V, Fini M, et al. A meta-analysis of biomarkers related to oxidative stress and nitric oxide pathway in migraine. Cephalalgia. 2015;35(10):931–937.
• 8. Powers SW, Coffey CS, Chamberlin LA, Ecklund DJ, Klingner EA, et al. Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine. N Engl J Med. 2017;376(2):115–24.
• 9. Hu C, Zhang Y, Tan G. Advances in topiramate as prophylactic treatment for migraine. Brain Behav. 2021;11(10):e2290.
• 10. Brandes JL, Saper JR, Diamond M, Couch JR, Lewis DW, et al. Topiramate for Migraine Prevention: A Randomized Controlled Trial. JAMA. 2004;291(8):965–73.
• 11. Censur D, Yılmaz D, Ardıçlı D, Censur H, Çelebi Tayfur A, et al. An Oxidative Stress Marker in Pediatric Migraine Patients: Dynamic Thiol-Disulfide Homeostasis. Turkish J Pediatr Dis. 2023;17(1):1–6.
• 12. Çevik MU, Yücel Y, Arıkanoğlu A, Varol S, Akıl E, et al. Serum levels of prolidase and ischemia modified albumin in patients with multiple sclerosis. J Clin Exp Investig. 2013;3(4):518–20.
• 13. Smith JA, Park S, Krause JS, Banik NL. Oxidative stress, DNA damage, and the telomeric complex as therapeutic targets in acute neurodegeneration. Neurochem Int. 2013;62(5):764–75.
• 14. Borkum JM. The Migraine Attack as a Homeostatic, Neuroprotective Response to Brain Oxidative Stress: Preliminary Evidence for a Theory. Headache J Head Face Pain [Internet]. 2018;58(1):118–35.
• 15. Ocal O, Ocal FD, Sinaci S, Daglar Z, Secen AE, et al. Maternal Serum and Fetal Cord Blood Concentrations of Thiol/ Disulfide and Ischemia-Modified Albumin as Predictors of Neural Tube Defects. Turk Neurosurg. 2023;33(1):134–9.
• 16. Carter JH, Sketris IS, Tamim HH, Levy AR, Langley JM. Prolidase Specificity as a diagnostic marker for breast cancer. J Popul Ther Clin Pharmacol. 2019;26(2):1–4.
• 17. Eren F, Koca Yozgat A, Firat Oğuz E, Neşelioğlu S, Firat R, et al. A New Perspective for Potential Organ Damage Due to Iron-Mediated Oxidation in Thalassemia Major Patients. J Clin Med. 2023;12(6):2422.
• 18. Say B, Dindar Badem N, Ergun U. Serum levels of ischemic modified albumin (IMA) and prolidase in migraine subjects. J Heal Sci Med. 2020;3(1):31–5.
• 19. Wilk P, Wątor E, Weiss MS. Prolidase – A protein with many faces. Biochimie. 2021;183:3–12
• 20. Bayraktar M, Bayraktar N. Prolidase. Göbeklitepe Int J Heal Sci. 2021;4:1–11.
• 21. Lai T, Chen L, Chen X, He J, Lv P, Ge H. Rhynchophylline attenuates migraine in trigeminal nucleus caudalis in nitroglycerin-induced rat model by inhibiting MAPK/NF-кB signaling. Mol Cell Biochem. 2019 461(1–2):205–12.
• 22. Pradhan AA, Smith ML, McGuire B, Tarash I, Evans CJ, Charles A. Characterization of a novel model of chronic migraine. PAIN®. 2014 Feb 1;155(2):269–74.
• 23. Narin F, Hanalioglu S, Ustun H, Kilinc K, Bilginer B. Topiramate as a neuroprotective agent in a rat model of spinal cord injury. Neural Regen Res. 2017;12(12):2071-76.
• 24. Moye LS, Tipton AF, Dripps I, Sheets Z, Crombie A, Violin JD, et al. Delta opioid receptor agonists are effective for multiple types of headache disorders. Neuropharmacology. 2019 Apr 1;148:77–86.
• 25. Harbeck H ‐T, Mentlein R. Aminopeptidase P from rat brain. Eur J Biochem. 1991;198(2):451–8.
• 26. Kapucu A, Kaptan Z, Akgun Dar K, Kaleler İ, Uzum G. Effects of Erythropoietin Pretreatment on Liver, Kidney, Heart Tissue in Pentylentetrazol-Induced Seizures; Evaluation in Terms of Oxidative Markers, Prolidase and Sialic Acid. J Ist Faculty Med. 2021;84(4):464–71.
• 27. Bar-Or D, Lau E, Winkler J V. A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia—a preliminary report. J Emerg Med. 2000 Nov 1;19(4):311–5.
• 28. Myara I, Charpentier C, Lemonnier A. Optimal conditions for prolidase assay by proline colorimetric determination: application to iminodipeptiduria. Clin Chim Acta. 1982 Oct 27;125(2):193–205.
• 29. Latif K, Khan AU, Izhar Ul Haque M, Naeem K. Bergapten Attenuates Nitroglycerin-Induced Migraine Headaches through Inhibition of Oxidative Stress and Inflammatory Mediators. ACS Chem Neurosci. 2021;12(18):3303–13.
• 30. Reuter U, Bolay H, Jansen-Olesen I, Chiarugi A, Del Rio MS, Letourneau R, et al. Delayed inflammation in rat meninges: implications for migraine pathophysiology. Brain. 2001;124(12):2490–502.
• 31. Uçkan K, Demir H, Demir C. Maternal serum ischemia-modified albumin (IMA), total-sulphydryl concentrations, and some subclinic inflammatory markers in hyperemesis gravidarum (HG). Taiwan J Obstet Gynecol. 2023 Jan 1;62(1):101–6.
• 32. Sbarouni E, Georgiadou P, Voudris V. Ischemia modified albumin changes - Review and clinical implications. Clin Chem Lab Med. 2011;49(2):177–84.
• 33. Kaefer M, Piva SJ, De Carvalho JAM, Da Silva DB, Becker AM, Coelho AC, et al. Association between ischemia modified albumin, inflammation and hyperglycemia in type 2 diabetes mellitus. Clin Biochem. 2010 Mar 1;43(4–5):450–4.
• 34. Turedi S, Gunduz A, Mentese A, Topbas M, Karahan SC, Yeniocak S, et al. The value of ischemia-modified albumin compared with d-dimer in the diagnosis of pulmonary embolism. Respir Res. 2008;9(1):1–12.
• 35. Aslan M, Nazligul Y, Horoz M, Bolukbas C, Bolukbas FF, Aksoy N, et al. Serum prolidase activity and oxidative status in Helicobacter pylori infection. Clin Biochem. 2007 Jan 1;40(1–2):37–40.
• 36. Delwing D, Bavaresco CS, Chiarani FA, Wannmacher CMD, Wajner M, Dutra-Filho CS, et al. In vivo and in vitro effects of proline on some parameters of oxidative stress in rat brain. Brain Res. 2003 Nov 21;991(1–2):180–6.
• 37. Yorns WR, Hardison HH. Mitochondrial Dysfunction in Migraine. Semin Pediatr Neurol. 2013 Sep 1;20(3):188–93.
• 38. Bütün A, Nazıroğlu M, Demirci S, Çelik Ö, Uğuz AC. Riboflavin and Vitamin E Increase Brain Calcium and Antioxidants, and Microsomal Calcium-ATP-ase Values in Rat Headache Models Induced by Glyceryl Trinitrate. J Membr Biol. 2015;248(2):205–13.
• 39. Cárdenas-Rodríguez N, Coballase-Urrutia E, Huerta-Gertrudis B, García-Cruz ME, Pedraza-Chaverri J, Coria-Jiménez R, et al. Antioxidant activity of topiramate: An antiepileptic agent. Neurol Sci. 2013 ;34(5):741–7.
• 40. Kubera M, Budziszewska B, Jaworska-Feil L, Basta-Kaim A, Leśkiewicz M, Tetich M, et al. Effect of topiramate on the kainate-induced status epilepticus, lipid peroxidation and immunoreactivity of rats. Pol J Pharmacol. 2004;56(5):553–61.
• 41. Armaǧan A, Kutluhan S, Yilmaz M, Yilmaz N, Bülbül M, Vural H, et al. Topiramate and vitamin e modulate antioxidant enzyme activities, nitric oxide and lipid peroxidation levels in pentylenetetrazol-induced nephrotoxicity in rats. Basic Clin Pharmacol Toxicol. 2008;103(2):166–70.
• 42. Muriach M, López-Pedrajas R, Barcia JM, Sanchez-Villarejo M V., Almansa I, Romero FJ. Cocaine causes memory and learning impairments in rats: involvement of nuclear factor kappa B and oxidative stress, and prevention by topiramate. J Neurochem. 2010;114(3):675–84.