Tarantula cubensis Ekstraktının Sıçanlarda Deneysel Akut Omurilik Yaralanması Üzerine Etkileri

Öz

Omurilik yaralanması (SCI), omurganın ciddi yaralanmalarından sonra ortaya çıkan kritik bir sağlık sorunudur. Bu çalışmada Tarantula cubensis ekstraktının akut dönemdeki olası etkileri değerlendirilmiştir. Sıçan travma modeli için 28 Sprague dawley kullanıldı. Tüm ratlar 4 gruba ayrıldı (n=7): Kontrol, hasar grubu (IG), prednizolon tedavisi (PG) ve Tarantula cubensis ekstraktı tedavisi (TCG). Kontrol grubu dışındaki tüm ratlara laminektomi uygulandı ve spinal korda 60 saniye anevrizma klempi uygulandı. Klinik iyileştirme değerlendirmesi, BBB (Basso, Beattie, Bresnahan Locomotor Rating Scale), histopatolojik (inflamatuar yanıt, nöron canlılığı) ve biyokimyasal değerlendirmede için 8- hydroxydeoxyguanosine (8-OHdG), myeloperoxidase (MPO), transforming growth faktör beta 1 (TGF β-1), tümor Nekroz Faktör Alfa (TNF-α), interleukin-2 (IL-2) değerlendirildi. Histopatolojik değerlendirmelere göre; TCG grubunda IG grubuna oranla daha az hasar ve inflamasyon gözlendi. TCG ve PG arasında istatistiksel olarak benzerlik vardı (p=0.005). BBB skoru TCG değerleri PG ve IG’ye göre yüksek bulundu. Laminektomi yapılan sıçanlarda MPO düzeyi TCG’de IG ve PG'den anlamlı düzeyde düşük bulundu (p=0.001). Antiinflamatuvar bir sitokin olan TGF β-1 (ng-l) TCG’de en yüksek seviyesinde ölçüldü (p=0.001). TNF-α (ng-l) seviyeleri TCG, PG ve IG'de kontrol grubuna göre daha yüksekti. Ancak kendi aralarında anlamlı bulunmamışlardır. IL-2 (ng-l) düzeyleri TCG, PG’de IG grubuna göre azalmıştı (p=0.05). Sonuç olarak; Tarantula cubensis ekstraktının antiinflamatuar aktivite göstererek omurilik dokusunda nöroprotektif etkisi olduğu belirlenmiştir.

Anahtar Kelimeler

• Antiinflamatuar etki
• Nöroproteksiyon
• Omurilik yaralanması
• Tarantula cubensis ekstraktı

Effects of Tarantula cubensis Extract on Experimental Acute Spinal Cord Injury in Rats

Öz

Spinal cord injury (SCI) is a critical health problem that occurs after spinal trauma. In this study, the possible effects of Tarantula cubensis extract in the acute period were evaluated. For the rat trauma model, 28 Sprague dawley rats were used. All rats were divided into 4 groups (n=7); Control, injury (IG), prednisolone treatment (PG), and Tarantula cubensis extract treatment (TCG). Laminectomy was applied to all rats except the control group, and an aneurysm clamp was applied to the spinal cord for 60 seconds. BBB (Basso, Beattie, Bresnahan Locomotor Rating Scale) for clinical improvement assessment, histopathological (inflammatory response, neuron viability), and the amount of biochemical parameters 8-hydroxydeoxyguanosine (8-OHdG), myeloperoxidase (MPO), transforming growth factor beta 1 (TGF β-1), tumor necrosis factor alpha (TNF-α), interleukin 2 (IL-2) were evaluated. According to histopathological evaluations; less damage and inflammation were observed in the TCG group compared to the IG group. There was a statistical similarity between TCG and PG (p=0.005) BBB score TCG values were higher than PG and IG rats. MPO level was found to be significantly lower than TCG group IG and PG in laminectomy rats (p=0.001). TGF β-1 (ng-l), which is an anti-inflammatory cytokine, was measured at the highest level of TCG (p=0.001). TNF-α (ng-l) levels were higher in TCG, PG, and IG compared to the control group. IL-2 (ng-l) levels were decreased in TCG, PG, and control groups compared to the IG group (p=0.05). Tarantula cubensis extract has been determined neuroprotective effect by showing anti-inflammatory activity.

Anahtar Kelimeler

• Anti-inflammatory effect
• Neuroprotection
• Spinal cord injury
• Tarantula cubensis extract

Kaynakça

1. Abe, K., Chu, PJ., Ishihara, A, Saito, H. Transforming growth factor-beta 1 promotes re- elongation of injured axons of cultured rat hippocampal neurons. Brain Res. 1996; 723(1-2): 206-209. doi: 10.1016/0006-8993(96)00253-3.
2. Aytar, MH., Civi, S., Kaymaz, M., Ergun, E., Kaymaz, FF., Pasaoglu, A. The Effect of Quetiapine on Treatment of Experimental Acute Spinal Cord Injury. Turk. Neurosurg. 2018; 28(1):105-110, doi: 10.5137/1019-5149.JTN.17476-16.1.
3. Basso, DM., Beattie, MS., Bresnahan, JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J. Neurotrauma 1995;12:1–21. doi: 10.1089/neu.1995.12.1
4. Bloom, O. Non-mammalian model systems for studying neuro-immune interactions after spinal cord injury. Exp. Neuro. 2014; 258: 130–140. doi: 10.1016/j.expneurol.2013.12.023
5. Boga, M., Discigil, B., Ozkisacik, EA., Gurcun, U., Badak, MI, et al. The combined effect of iloprost and N-acetylcysteine in preventing spinal cord ischemia in rabbits. European Journal of Vascular and Endovascular Surgery 2006; 31: 366–372. doi:10.1016/j.ejvs.2005.10.027
6. Bracken, MB., Shepard, M., Collins, WF., Holford, TR., Baskin, DS., Eisenberget, HM., et al. Methylprednisoloneor naloxone treatment after acute spinal injury: 1-year follow-up data. Results of the Second National Acute Spinal Cord Injury Study. J. Neurosurg. 1992;76: 23-31. doi: 10.3171/jns.1992.76.1.0023
7. Chehrehasa, F., Cobcroft, M., Young, YW., Mackay-Sim, A., Goss, B. An acute growth factor treatment that preserves function after spinal cord contusion injury. J. Neurotrauma 2014;31(21):1807-1813. doi: 10.1089/neu.2013.3294
8. Chirumbolo, S., Bjørklund, G. Homeopathic Dilutions, Hahnemann Principles, and the Solvent Issue: Must We Address Ethanol as a “Homeopathic” or a “Chemical” Issue? Homeopathy 2018; 107 (01): 040-044. doi: 10.1055/s-0037-1608898

9. Coskun, D. Veterinary Supportive Therapy: Tarantula Cubensis Alcoholic Extract, InactivedParapoxvirus Ovis and Corynebacterium Cutis Lysate, Dicle Üniv Vet Fak Derg 2017;10(1):30-3
10. Conover, WJ. Practical Nonparametric Statistics. 2nd Edition, 1980, John Wiley & Sons, New York.
11. Gensel, JC., Zhang, B. Macrophage activation and its role in repair and pathology after spinal cord injury. Brain Res. 2015;1619:1-11. doi:10.1016/j.brainres.2014.12.045
12. Geremia, NM., Bao, F., Rosenzweig, TE., Hryciw, T., Weaver, L., et al. CD11d antibody treatment improves recovery in spinal cord-injured mice. J. Neurotrauma. 2012; 29(3): 539–550. doi: 10.1089/neu.2011.1976
13. Geremia, NM., Hryciwa, T., Baoa, F., Streijger, F., Okonb, E., Lee, JHT., et al. The effectiveness of the anti-CD11d treatment is reduced in ratmodels of spinal cord injury that produce significant levels of intraspinal hemorrhage. Exp. Neurol. 2017; 295:125-134.doi: 10.1016/j.expneurol.2017.06.002
14. Gris, D., Hamilton, EF., Weaver, LC. The systemic inflammatory response after spinal cord injury damages lungs and kidneys. Exp. Neurol. 2008; 211(1): 259-270. doi: 10.1016/j.expneurol.2008.01.033
15. Gul Satar, NY., Cangul, IT., Topal, A., Kurt, H., Ipek, V., & Onel, GI. The effects of Tarantula cubensis venom on open wound healing in rats. Journal of wound care, 2017. 26(2), 66–71. https://doi.org/10.12968/jowc.2017.26.2.66
16. Kakulas BA. Pathology of spinal injuries. 1984; Cent. Nerv. Syst. Trauma 1, 117±129. Karabacak, M., Eraslan, G., Kanbur, M., Sarıca, ZS. Effects of Tarantula cubensis D6 on aflatoxin-induced injury in biochemical parameters in rats. Homeopathy 2015;104(3):205-210. doi: 10.1016/j.homp.2015.02.005
17. Kizilay, Z., Aktas, S., Cetin, NK., Kılıc, MA., Oztürk, H. Effect of Tarantula Cubensis Extract (Theranekron) on Peripheral Nerve Healing in an Experimental Sciatic Nerve Injury Model in Rats. Turk. Neurosurg. 2019; 29(5):743-749. doi: 10.5137/1019-5149.JTN.26162-19.2
18. Klempt, ND., Sirimanne, E., Gunn, AJ., Klempt, M., Singh, K., Williams, C., et al. Hypoxia-ischemia induces transforming growth factor-/31 mRNA in the infant rat brain. Mol. Brain Res. 1992; 13(1-2): 93-101. doi: 10.1016/0169-328X(92)90048-G
19. McDonald, JW., Sadowsky, C. Spinal-cord injury. Lancet. 2002;359(9304):417-425. doi:10.1016/S0140-6736(02)07603-1
20. Munter, JP., Beugels, J., Munter, S., Jansen, L., Cillero-Pastor, B., Moskvin, O., et al. Standardized human bone marrow-derived stem cells infusion improves survival and recovery in a rat model of spinal cord injury. J. Neurol. Sci. 2019;402:16-29. doi: 10.1016/j.jns.2019.05.002
21. Rivlin, AS., Tator, CH. Effect of duration of acute spinal cord compression in a new acute cord injury model in the rat. Surg. Neurol. 1978; 10 (1):38-43.
22. Salarinia, R., Sadeghnia, HR., Alamdari, DH., Hoseini, SJ., Mafinezhad, A., Hosseini, M. Platelet rich plasma: Effective treatment for repairing of spinal cord injury in rat. Acta Orthop. Traumatol. Turc. 2017;51(3):254-257. doi: 10.1016/j.aott.2017.02.009
23. Sultan, I., Lamba N., Liew, A., Doung, P., Tewarie, I., Amamoo, JJ., et al. The safety and efficacy of steroid treatment for acute spinal cord injury: A Systematic Review and meta-analysis. Heliyon 2020; 6(2): e03414. doi: 10.1016/j.heliyon.2020.e03414.
24. Tator, CH., Koyanagi, I. Vascular mechanisms in the pathophysiology of human spinal cord injury. J. Neurosurg. 1997; 86 (3): 483-492. doi: 10.3171/JNS.1997.86.3.0483
25. Wallace, MC., Tator, CH., Lewis, AJ. Chronic regenerative changes in the spinal cord after cord compression injury in rats. 1987, Surgical. Neurology 1987; 27 (3): 209-219. doi: 10.1016/0090-3019(87)90031-0
26. Walters, BC., Hadley, N., Hurlbert, RJ., Aarabi, B., Dhall, SS., Gelb, DE., et al. Guidelines for the management of acute cervical spine and spinal cord injuries. 2013 update. Neurosurgery 2013; 60 ( Suppl. 1): 82–91. doi: 10.1227/01.neu.0000430319.32247.7f
27. Yuksel, U., Bakar, B., Dincel, GC., Yildiran, FAB., Ogden, M., Kisa, U. The Investigation of the Cox-2 Selective Inhibitor Parecoxib Effects in Spinal Cord Injury in Rat. J Invest Surg. 2019; 32(5):402-413. doi: 10.1080/08941939.2017.1423423
28. Zaminy, A., Shokrgozar, MA., Sadeghi, Y., Norouzian, M., Heidari, HM., Piryaei, A. Transplantation of Schwann Cells Differentiated from Adipose Stem Cells Improves Functional Recovery in Rat Spinal Cord Injury. Arch. Iran. Med. 2013;6(9):533-541.
29. Zhang, Y., Liu, Z., Zhang, W., Wu, Q., Zhang, Y., Liu, Y., et al. Melatonin improves functional recovery in female rats after acute spinal cord injury by modulating polarization of spinal microglial/macrophages. J. Neurosci. Res. 2019;97(7):733-743. doi: 10.1002/jnr.24409.