Hidrojen sülfür, karbon monoksit ve nitrik oksidin sıçanlarda pentilentetrazol indüklü nöbetler üzerindeki etkileri

Year 2020, Volume: 15 Issue: 3, 1 - 6, 16.10.2020

Ezgi Eroğlu Çiğdem Çengelli Ünel Nuşin Harmancı Zuhal Kaltuş Cansu Kılıç Hatice Doğan Rabiye Altınbaş Kevser Erol

https://doi.org/10.17517/ksutfd.681282

Abstract

Amaç: Sıçanlarda pentilentetrazol indüklü konvülsiyonlarda biyoaktif gaz mediyatörler hidrojen sülfür (H2S), karbon monoksid (CO) ve nitrik oksid (NO)'in anti-konvülsan etkilerinin araştırılması amaçlanmıştır.
Gereç Yöntem: Seksen erkek Wistar-Albino sıçan rastgele on gruba ayrılmıştır. Konvülsiyonlar, intraperitonal olarak verilen 60 mg/kg pentilentetrazol ile indüklendi. Pentilentetrazolden 60 dakika sonra Diazepam, NaHS, CORM-2, L-arginin ve L-NAME uygulandı. Nöbet latensi, nöbet süresi ve nöbet skoru değerlendirildi. Veriler Kruskal Wallis testi ve ardından Tukey ile analiz edildi. P <0.05 istatistiksel olarak anlamlı kabul edildi.
Bulgular: Diazepam (2 mg/kg) nöbet latensini uzattı, diğer gruplarda ise anlamlı bir fark bulunmadı. Diazepam (1 ve 2 mg/kg) ve NaHS (10 mg/kg) nöbet süresini azalttı. NaHS (5 mg/kg), CORM-2 (5 ve 10 mg/kg), L-Arjinin (30 ve 100 mg / kg) ve L-NAME (30 mg / kg), nöbet skorunu diazepam ile karşılaştırıldığında önemli ölçüde artırdı.
Sonuç: NaHS (10 mg/kg) pentilentetrazole bağlı nöbetlerde koruyucu olabilir.

Keywords

epilepsi, hidrojen sülfür, karbon monoksid, nitrik oksid, nöbetler

Supporting Institution

Eskişehir Osmangazi Üniversitesi Tıp Fakültesi Bilimsel Araştırma Projeleri Komisyonu

Project Number

2019/11D05

The effects of hydrogen sulfide, carbon monoxide and nitric oxide on pentylenetetrazole-induced seizures in rats

Abstract

Objective: It is aimed to investigate the anti-convulsant effects of bioactive gas mediators hydrogen sulfide (H2S), carbon monoxide (CO) and nitric oxide (NO) in pentylenetetrazole-induced convulsions in rats.
Material Methods: Eighty male Wistar-Albino rats randomly divided into ten groups. Convulsions was induced by administering 60 mg/kg pentylentetrazole intraperitonally. Diazepam, NaHS, CORM-2, L-arginine and L-NAME were administred 60 minutes after pentylentetrazole. Seizure latency, seizure duration and seizure score were evaluated. Data were analyzed by the Kruskal Wallis test followed by posthoc analyses with Tukey. P <0.05 was considered statistically significant.
Results: Diazepam (2 mg/kg) extended the seizure latency and no significant difference was found in other groups. Diazepam (1 and 2 mg/kg) and NaHS (10 mg/kg) reduced seizure duration. NaHS (5 mg/kg), CORM-2 (5 and 10 mg/kg), L-arginine (30 and 100 mg/kg) and L-NAME (30 mg/kg) increased the seizure score significantly as compared to diazepam (1 and 2 mg/kg) groups.
Conclusion: NaHS (10 mg/kg) may be protective in pentylentetrazole-induced seizures.

Keywords

epilepsy, hydrogen sulfide, carbon monoxide, nitric oxide, seizures

Project Number

2019/11D05

References

• 1. Stafstrom CE, Carmant L. Seizures and epilepsy: an overview for neuroscientists. Cold Spring Harb Perspect Med. 2015;5(6).
• 2. Singh A, Trevick S. The Epidemiology of Global Epilepsy. Neurol Clin. 2016;34(4):837-47.
• 3. Laxer KD, Trinka E, Hirsch LJ, Cendes F, Langfitt J, Delanty N, et al. The consequences of refractory epilepsy and its treatment. Epilepsy Behav. 2014;37:59-70.
• 4. Newton RW. When is drug treatment not necessary in epilepsy? Factors that should influence the decision to prescribe. J R Soc Med. 2004;97(1):15-9.
• 5. Lazarini-Lopes W, Do Val-da Silva RA, da Silva-Junior RMP, Leite JP, Garcia-Cairasco N. The anticonvulsant effects of cannabidiol in experimental models of epileptic seizures: from behavior and mechanisms to clinical insights. Neurosci Biobehav Rev. 2020.
• 6. Johannessen SI, Landmark CJ. Antiepileptic drug interactions - principles and clinical implications. Curr Neuropharmacol. 2010;8(3):254-67.
• 7. Loscher W. Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs. Seizure. 2011;20(5):359-68.
• 8. Samokhina E, Samokhin A. Neuropathological profile of the pentylenetetrazol (PTZ) kindling model. Int J Neurosci. 2018;128(11):1086-96.
• 9. Li B, Wang L, Sun Z, Zhou Y, Shao D, Zhao J, et al. The anticonvulsant effects of SR 57227 on pentylenetetrazole-induced seizure in mice. PLoS One. 2014;9(4):e93158.
• 10. Farrugia G, Szurszewski JH. Carbon monoxide, hydrogen sulfide, and nitric oxide as signaling molecules in the gastrointestinal tract. Gastroenterology. 2014;147(2):303-13.
• 11. Shefa U, Yeo SG, Kim MS, Song IO, Jung J, Jeong NY, et al. Role of Gasotransmitters in Oxidative Stresses, Neuroinflammation, and Neuronal Repair. Biomed Res Int. 2017;2017:1689341.
• 12. Shefa U, Kim D, Kim MS, Jeong NY, Jung J. Roles of Gasotransmitters in Synaptic Plasticity and Neuropsychiatric Conditions. Neural Plast. 2018;2018:1824713.
• 13. Yang ZX, Qin J, Du JB, Chang XZ, Han Y. [Effect of endogenous heme oxygenase-carbon monoxide on brain damage induced by recurrent febrile seizures]. Zhonghua Er Ke Za Zhi. 2005;43(4):252-5.
• 14. Luo Y, Wu PF, Zhou J, Xiao W, He JG, Guan XL, et al. Aggravation of seizure-like events by hydrogen sulfide: involvement of multiple targets that control neuronal excitability. CNS Neurosci Ther. 2014;20(5):411-9.
• 15. Herberg LJ, Grottick A, Rose IC. Nitric oxide synthesis, epileptic seizures and kindling. Psychopharmacology (Berl). 1995;119(1):115-23.
• 16. Osonoe K, Mori N, Suzuki K, Osonoe M. Antiepileptic effects of inhibitors of nitric oxide synthase examined in pentylenetetrazol-induced seizures in rats. Brain Res. 1994;663(2):338-40.
• 17. Buisson A, Lakhmeche N, Verrecchia C, Plotkine M, Boulu RG. Nitric oxide: an endogenous anticonvulsant substance. Neuroreport. 1993;4(4):444-6. 18. de Oliveira CC, de Oliveira CV, Grigoletto J, Ribeiro LR, Funck VR, Grauncke AC, et al. Anticonvulsant activity of beta-caryophyllene against pentylenetetrazol-induced seizures. Epilepsy Behav. 2016;56:26-31.
• 19. Kang X, Shen X, Xia Y. Electroacupuncture-induced attenuation of experimental epilepsy: a comparative evaluation of acupoints and stimulation parameters. Evid Based Complement Alternat Med. 2013;2013:149612.
• 20. Dhir A, Rogawski MA. Determination of minimal steady-state plasma level of diazepam causing seizure threshold elevation in rats. Epilepsia. 2018;59(5):935-44.
• 21. Polhemus DJ, Lefer DJ. Emergence of hydrogen sulfide as an endogenous gaseous signaling molecule in cardiovascular disease. Circ Res. 2014;114(4):730-7.
• 22. Panthi S, Manandhar S, Gautam K. Hydrogen sulfide, nitric oxide, and neurodegenerative disorders. Transl Neurodegener. 2018;7:3.
• 23. Leffler CW, Parfenova H, Jaggar JH, Wang R. Carbon monoxide and hydrogen sulfide: gaseous messengers in cerebrovascular circulation. J Appl Physiol (1985). 2006;100(3):1065-76.
• 24. Hu LF, Lu M, Hon Wong PT, Bian JS. Hydrogen sulfide: neurophysiology and neuropathology. Antioxid Redox Signal. 2011;15(2):405-19.
• 25. Kimura H, Nagai Y, Umemura K, Kimura Y. Physiological roles of hydrogen sulfide: synaptic modulation, neuroprotection, and smooth muscle relaxation. Antioxid Redox Signal. 2005;7(5-6):795-803.
• 26. Abe K, Kimura H. The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci. 1996;16(3):1066-71.
• 27. Tang G, Wu L, Wang R. Interaction of hydrogen sulfide with ion channels. Clin Exp Pharmacol Physiol. 2010;37(7):753-63.
• 28. Otterbein LE. Carbon monoxide: innovative anti-inflammatory properties of an age-old gas molecule. Antioxid Redox Signal. 2002;4(2):309-19.
• 29. Otterbein LE, Soares MP, Yamashita K, Bach FH. Heme oxygenase-1: unleashing the protective properties of heme. Trends Immunol. 2003;24(8):449-55.
• 30. Fredenburgh LE, Merz AA, Cheng S. Haeme oxygenase signalling pathway: implications for cardiovascular disease. Eur Heart J. 2015;36(24):1512-8.
• 31. Joshi HP, Kim SB, Kim S, Kumar H, Jo MJ, Choi H, et al. Nanocarrier-mediated Delivery of CORM-2 Enhances Anti-allodynic and Anti-hyperalgesic Effects of CORM-2. Mol Neurobiol. 2019;56(8):5539-54.
• 32. Al-Huseini LM, Aw Yeang HX, Hamdam JM, Sethu S, Alhumeed N, Wong W, et al. Heme oxygenase-1 regulates dendritic cell function through modulation of p38 MAPK-CREB/ATF1 signaling. J Biol Chem. 2014;289(23):16442-51.
• 33. Crespy D, Landfester K, Schubert US, Schiller A. Potential photoactivated metallopharmaceuticals: from active molecules to supported drugs. Chem Commun (Camb). 2010;46(36):6651-62.
• 34. Queiroga CS, Vercelli A, Vieira HL. Carbon monoxide and the CNS: challenges and achievements. Br J Pharmacol. 2015;172(6):1533-45.
• 35. Zimmermann A, Leffler CW, Tcheranova D, Fedinec AL, Parfenova H. Cerebroprotective effects of the CO-releasing molecule CORM-A1 against seizure-induced neonatal vascular injury. Am J Physiol Heart Circ Physiol. 2007;293(4):H2501-7.
• 36. Banach M, Piskorska B, Czuczwar SJ, Borowicz KK. Nitric oxide, epileptic seizures, and action of antiepileptic drugs. CNS Neurol Disord Drug Targets. 2011;10(7):808-19.
• 37. Jelenkovic A, Jovanovic M, Ninkovic M, Maksimovic M, Bokonjic D, Boskovic B. Nitric oxide (NO) and convulsions induced by pentylenetetrazol. Ann N Y Acad Sci. 2002;962:296-305.