NİGELLA SATİVA EKSTRESİNİN CAS: 490-91-5 DENEYSEL SUBARAKNOİD KANAMAYA BAĞLI VASKÜLER DEĞİŞİKLİKLER ÜZERİNE OLAN ETKİSİNİN IŞIK MİKROSKOBİK VE STEREOLOJİK İNCELENMESİ

Year 2022, Volume: 1 Issue: 2, 29 - 39, 31.07.2022

Mehmet Kürşad Karadağ Hakan Hadi Kadıoğlu

Abstract

Amaç: Bu çalışmada Nigella Sativa Ekstresinin CAS:490-91-5, ratlarda oluşturulan deneysel subaraknoid kanama modelinde vazospazm üzerine etkileri incelendi. Gereç ve Yöntem: 60 adet erkek Wistar cinsi albino rat, altı gruba ayrıldı. Grup 1 (kontrol), grup 2 (sham), grup 3 (subaraknoid kanama sonrası birinci saatte dekapitasyon), grup 4 (subaraknoid kanama sonrası 48.saatte dekapitasyon), grup 5 (subaraknoid kanama öncesi thymoquinone verilip, 6 saat sonrasında subaraknoid kanama oluşturulup bundan 1 saat sonra dekapitasyon) ve grup 6 (subaraknoid kanama sonrası birinci, 24. ve 48.saatlerde thymoquinone verilip sonrasında dekapitasyon) olarak tanzim edildi. Atatürk Üniversitesi Tıp Fakültesi Biyokimya Laboratuvarı’nda dimetil sülfoksit yardımı ile dilüe edilerek hazırlanan thymoquinone, 5mg/kg dozunda intraperitoneal yolla verildi. İşlem sırasında 8 adet rat kaybı oldu. Kalan 52 adet ratın dekapitasyon işlemi sonrasında baziler arterlerin lümen alanları ve duvar kalınlıkları stereolojik yöntemle histopatolojik olarak incelendi. Bulgular: Subaraknoid kanama öncesi tek doz verilen (grup5) ve subaraknoid kanama sonrası 3 gün thymoquinone verilen (grup6) grupların her ikisi de hiç thymoquinone verilmeyen (grup3) gruba göre baziller arter lümen alanlarında genişleme istatistiksel olarak anlamlıdır. Arter duvar kalınlıkları thymoquinone verilen (grup6 ve grup5) gruplar ile thymoquinone verilmeyenler (grup3, grup4) arasındaki fark istatistiksel olarak anlamlı bulunmuştur. Bu sonuç bize ilaç verilme ve verilmeme durumu arasında duvar kalınlığı açısından farklılık olduğunu ortaya koymuş, ilaç verilen gruplarda duvar kalınlığı azalmıştır. Sonuç: Bu çalışmada elde edilen bulgular, thymoquinone’nun ratlarda subaraknoid kanama sonrası vazospazmı önleyici olabileceğini göstermektedir

Keywords

Nigella Sativa Ekstresi CAS:490-91-5, stereoloji, subaraknoid kanama, vazospazm

THE STEREOLOGICAL AND LIGHT MICROSCOPY INVESTIGATION OF THE EFFECT OF NIGELLA SATIVA EXTRACT CAS: 490-91-5 ON VASCULAR CHANGES IN EXPERIMENTAL SUBARACHNOID HEMORRHAGE MODEL

Abstract

Objective: In this study, the effect of Nigella Sativa Extract CAS: 490-91-5 The effects on vasospasm in rats was investigated in an experimental subarachnoid hemorrhage model. Material and Method: 60 male Wistar albino rats were divided into 6 groups as follows; Group 1 (control), group 2 (sham), group 3 (decapitation, one hour after subarachnoid hemorrhage), group 4 (decapitation, 48 hours after subarachnoid hemorrhage), group 5 (6 hours prior to subarachnoid hemorrhage thymoquinone injection and one hour later after subarachnoid hemorrhage decapitation), group 6 (thymoquinone injection 1, 24 and 48 hours later subarachnoid hemorrhage and decapitation after the last injection). Thymoquinone that was prepared in the Atatürk University Biochemistry Laboratory via dilatation of dimethyl sulfoxide was injected intraperitoneally with the dose of 5mg/kg to the rats. 8 rats died during the procedure. The basilar artery lumen size and wall thickness of the remaining 52 rats were investigated with a stereological histopathologically approach after decapitation. Results: The widening of basilar artery lumen of group 5 (one dose of thymoquinone) and group 6 (3 doses of thymoquinone after subarachnoid hemorrhage) is statistically significantly increased than group 3 (no thymoquinone injection). The difference of artery wall thicknesses between thymoquinone injected groups (5 and 6) and non-thymoquinone injected groups (3-4) are also statistically significant. This result indicates that the thymoquinone effectively makes a significant difference to the wall thickness, thymoquinone injected groups have decreased wall thickness. Conclusion: The result of this study shows that thyquinone scans prevents vasospasm related to subarachnoid hemorrhage. Further studies that use this agent in clinical trials are needed to show the clinical effects of thymoquinone.

Keywords

Nigella Sativa Extract CAS: 490-91-5, stereology, subarachnoid hemorrhage, vasospasms

References

• Referans1. Weir B. (ed)Subarachnoid Hemorrhage: Causes and cures. Oxford University Press. NY. 1998; 144-176
• Referans2. Bederson JBi Connoly ES, Batjer HH, et al. Guidelines for the manangement of aneurysmal subarachnoid hemorrhage. A statement for Healthcare Professionals from a Special Writing Group of the Stroke Council, American Heart Association. Stroke 2009; 40: 994-1025
• Referans3. Kocaeli H, Korfalı E. Anevrizmal subaraknoid kanama ve komplikasyonları. Temel Nöroşirurji. Korfalı E, Zileli M (ed). Türk Nöroşirurji Derneği Yayınları, Ankara, 2010, sayfa 803-814
• Referans4. De Rooij NK, Linn FH, van der Plas JA, et al. Incidence of subarachnoid haemorrhage: a systematic review with emphasis on region, age, gender and time trends. J Neurol Neurosurg Psychiatry. 2007 Dec; 78(12): 1365-72.
• Referans5. Van Gijn J, Kerr RS, Rinkel GJ. Subarachnoid haemorrhage. Lancet 2007; 369: 306-18
• Referans6. Findlay JM. Cerebral Vasospasm in Youmans’ Neurological Surgergy, Winn HR(ed), Elsevier, Philedelphia 2014, sayfa 3791-3800
• Referans7. Eisenhut M. Vasospasm in cerebral inflammation. Int J Inflam. 2014;2014: 509-707
• Referans8. Cook DA, Volrath B: Free radicals and intracelluler events associated with cerebrovascular spasm. Cardiovasc Res 1995; 30: 493-500
• Referans9. Ali BH, Blunden G. Pharmacological and toxicological properties of Nigella Sativa. Phytother. Res. 2003; 17: 299-305
• Referans10. Taborsky J, Kunt M, Kloucek P, et al. Identification of potential sources of thymoquinone and related compounds in Asteraceae, Cupressaceae, Lumiaceae, and Ranunculaceae families. Cent Eur J Chem. 2012; 10: 1899-1906
• Referans11. Mansour MA, Nagi MN, El-Khatib AS, et al. Effects of thymoquinone on antioxidant enzyme activities, lipid peroxidation and DT-diaphorase in diffirent tissues of mice a possible mechanism of action. Cell Biochem Funct 2002; 20: 143-151
• Referans12. Vaillancourt F, Silva P, Shi Q, et al. Elucidation of molecular mechanisms underlying the protective effects of thymoquinone against rheumatoid arthritis. J Cell Biochem. 2011; 112: 107-117
• Referans13. Marbacher S, Fandino J, Kitchen ND. Standard intracranial in vivo animal models of delayed cerebral vasospasm. Br J Neurosurg. 2010; 24: 415-34
• Referans14. Barry KJ, Gogjian MA, Stein BM. Small animal model for investigation of subarachnoid hemorrhage and cerebral vasospasm. Stroke. 1979; 10: 538-41.
• Referans15. Sasaki T, Wakai S, Asano T, Watanabe T, Kirino T, Şano K. The effect of a lipid hydroperoxide of arachidonic acid on the canine basilar artery. An experimental study on cerebral vasospasm. J Neurosurgery. 1981;54: 357-365.
• Referans16. Mills JN, Mehta V, Russin J, et al. Advanced imaging modalities in the detection of cerebral vasospasm. Neurol Res İnt. 2013;2013:415960.
• Referans17. Findlay JM: Cerebral vasospasm in Youmans’ Neurological Surgery, Winn HR (ed), Elsevier, Philedelphia 2014; sayfa: 3791-3800
• Referans18. Haley EC Jr, Kassell NF, Apperson-Hansen C, Maile MH, Alves WM: A randomized, double blind, vehicle controlled trial of tirilazad mesylate in patients with aneurismal subarachnoid hemorrhage: A cooperative study in North America. J neurosurg 1997;86: 467-474
• Referans19. Bowman G, Bonneau RH, Chinchilli VM, Tracey KJ, Cockroft KM. A novel inhibitor of inflammatory cytokine production(CNI-1493) reduces rodent post- hemorrhagic vasospasm. Neurocrit Care. 2006; 5: 222-9
• Referans20. Gallia GL, Tamargo RJ. Leukocyte-endothelial cell interactions in chronic vasospasm after subarachnoid hemorrhage. Neurol Res. 2006; 28: 750-8
• Referans21. Zhou ML, Shi JX, Hang CH, Cheng HL, Qi XP, Mao L, Chen KF, Yin HX. Potential contribution of nuclear factor-kappa B to cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits. J Cereb Blood Flow Metab. Feb 7 2007.
• Referans22. Misra HP, Fridovich I. The generation of superoxide radical during the autooxidation of hemoglobin. J Biol Chem 1972; 10: 6960-62
• Referans23. Grasso G: An overview of new pharmacological treatments for cerebrovascular dysfunction after experimental subarachnoid hemorrhage. Brain Res Brain Res Rev 2004; 44 : 49-63
• Referans24. Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobaya-shi M, Mitsui Y. A novel potent vasocontrictor peptide pro-duced by vascular endothelial cells. Nature 1988;332:411-5.
• Referans25. Badary OA, Taha RA, Gamal El-Din AM, et al. Thymoquinone is a potent superoxide anion scavenger. Drug Chem Toxicol 2003; 26: 87-98
• Referans26. Darakhshan S, Pour AB, Colagar AH, Sisakhtnezhad S, et al. Tyhmoquinone and its therapeutic potentials. Pharmacological Research. 2015; 95-96: 138-158.
• Referans27. Salem ML. Immunomodulatory and therapeutic properties of the Nigella sativa seed. Int Immunopharmacol. 2005; 5: 1749-1770
• Referans28. Solomon RA, Antunes JL, Chen RY, et al. Decrease in cerebral blood flow in rats after experimental subarachnoid hemorrhage: a new animal model. Stroke. 1985; 16: 58-64.
• Referans29. Sen J, Belli A, Albon H, Morgan L, Petzold A, Kitchen N. Triple-H therapy in the management of aneurysmal subarachnoid haemorrhage. Lancet Neurol. 2003; 2: 614- 621
• Referans30. Roos YB, Levi M, Carroll TA, et al. Nimodipine increases fibrinolytic activity in patients with aneurysmal subarachnoid hemorrhage. Stroke. 2001; 32: 1860-2.
• Referans31. Linfante I, Delgado-Mederos R, Andreone V, et al. Angiographic and hemodynamic effect of high concentration of intra-arterial nicardipine in cerebral vasospasm. Neurosurgery. 2008;63: 1080-6; discussion 86-7.
• Referans32. Lannes M, Teitelbaum J, del Pilar Cortes M, et al. Milrinone and hemeostasis to treat cerebral vasospasm associated with subarachnoid hemorrhage: the Montreal Neurological Hospital Protocol. Neurocrit Care.2012;16: 354-62
• Referans33. McGirt MJ, Blessing R, Alexander MJ, et al. Risk of cerebral vasopasm after subarachnoid hemorrhage reduced by statin therapy: A multivariate analysis of an institutional experience. J Neurosurg. 2006; 105: 671-4.
• Referans34. Huang D, Shenoy A, Cui J, et al. In situ detection of AP sites and DNA strand breaks bearing 3'-phosphate termini in ischemic mouse brain. FASEB J. 2000; 14: 407-17.
• Referans35. Bautista C. Unresolved issues in the management of aneurysmal subarachnoid hemorrhage. AACN Adv Crit Care. 2012; 23: 175-85.
• Referans36. Dalbasti T, Karabiyikoglu M, Ozdamar N, et al. Efficacy of controlled-release papaverine pellets in preventing symptomatic cerebral vasospasm. J Neurosurg. 2001; 95: 44-5