Sıçanlarda alt ekstremite iskemi reperfüzyon hasarında farklı amantadin dozlarının akciğer dokusu üzerine etkileri

Year 2022, , 551 - 557, 30.12.2022

Nevcihan Şahutoğlu Bal , Ayça Taş Tuna , Ali Bal , Onur Palabıyık , Özcan Budak , Hüseyin Çakıroğlu , Sezen Irmak Gözükara

https://doi.org/10.18663/tjcl.1181097

Abstract

Amaç: İskemi/reperfüzyon (İ/R) hasarı abdominal aort cerrahisi sonrası sık görülen bir komplikasyondur. N-Metil D-Aspartat (NMDA) antagonistleri birçok organı İ/R hasarına karşı korur. Bu nedenle bu çalışmada, sıçanlarda alt ekstremite İ/R hasarı sonrası 135 mg/kg ve 90 mg/kg amantadinin akciğer dokusu üzerindeki etkilerini araştırmayı amaçladık.
Gereç ve Yöntemler: 36 wistar sıçan rastgele her biri altı sıçan içeren 6 gruba ayrıldı; Sham grubu (Grup S), Amantadin 90 grubu (Grup A-90), Amantadin 135 grubu (Grup A-135), İskemi/Reperfüzyon grubu (Grup İ/R), İskemi/Reperfüzyon + Amantadin 90 grubu (Grup İ/R-A 90), İskemi/Reperfüzyon + Amantadin 135 grubu (Grup İ/R-A 135). İşlem sonunda tüm ratlar sakrifiye edilerek akciğer dokuları alındı. Akciğer dokuları biyokimyasal ve histopatolojik olarak incelendi.
Bulgular: Gruplar arasında akciğer dokusu katalaz, süperoksit dismutaz aktiviteleri ve malondialdehit seviyeleri benzerdi. Akciğer dokusu nötrofil/lenfosit infiltrasyon skoru Grup İ/R'de Grup S, Grup A-90 ve Grup A-135'e göre daha yüksekti. Alveolar duvar kalınlaşma skoru Grup İ/R'de Grup S, Grup A-90, Grup A-135 ve Grup İ/R-A 135'e göre daha yüksekti.
Sonuçlar: Akciğer dokusu biyokimyasal değerleri arasında istatistiksel olarak anlamlı bir fark bulamasak da akciğer dokusunun histopatolojik olarak İ/R hasarından etkilendiğini ve amantadin kullanımı ile hasarın daha az olduğunu gözlemledik. İ/R hasarının azaltılmasında 135 mg/kg amantadin uygulaması 90 mg/kg'dan daha faydalı olmuştur.

Keywords

amantadin, iskemi reperfüzyon hasarı, alt ekstremite, akciğer dokusu

Supporting Institution

Sakarya Universitesi BAP

Project Number

2019-7-25-29

The effects of different doses of amantadine on lung tissue in lower extremity ischemia reperfusion injury in rats

Abstract

Aim: Ischemia/reperfusion (I/R) injury is a common complication after abdominal aortic surgery. N-Methyl D-Aspartate (NMDA) antagonists protect many organs against to I/R injury. Therefore, in this study, we aimed to investigate the effects of 135 mg/kg and 90 mg/kg of amantadine, on lung tissue after lower extremity I/R injury in rats.
Material and Methods: 36 wistar rats were randomly divided into 6 groups each containing six rats as follows; Sham group (Group S), Amantadine 90 group (Group A-90), Amantadine 135 group (Group A-135), Ischemia/Reperfusion group (Group I/R), Ischemia/Reperfusion + Amantadine 90 group (Group I/R-A 90), Ischemia/Reperfusion + Amantadine 135 group (Group I/R-A 135). At the end of procedure, all rats were sacrificed, and their lung tissues were obtained. Lung tissues were examined biochemical and histopathologically.
Results: The lung tissue catalase, superoxide dismutase activities and malondialdehide levels were similar between the groups. Lung tissue neutrophil/lymphocyte infiltration score levels were higher in Group I/R than Group S, Group A-90 and Group A-135. Alveolar wall thickening score levels were higher in Group I/R than Group S, Group A-90, Group A-135 and Group I/R-A 135.
Conclusion: Although we could not find a statistically significant difference between lung tissue biochemical values, we observed that lung tissue was histopathologically affected by I/R damage and the damage was less with amantadine use. In the reduction of I/R damage, 135 mg/kg administration of amantadine was more beneficial than 90 mg/kg.

Keywords

amantadine; ischemia reperfusion injury; lower extremity, lung tissue

Project Number

2019-7-25-29

References

• 1. Yardim-Akaydin S, Sepici A, Ozkan Y, Simşek B, Sepici V. Evaluation of allantoin levels as a new marker of oxidative stress in Behçet's disease. Scand J Rheumatol 2006;35:61-4.
• 2. Yassin MM, Harkin DW, BarrosD'Sa AA, Halliday MI, Rowlands BJ. Lower limb ischemia-reperfusion injury triggers a systemic inflammatory response and multiple organ dysfunction. World J Surg 2002;26:115-21.
• 3. Himmelseher S, Durieux ME. Revising a dogma: ketamine for patients with neurological injury? Anesth Analg 2005;101:524-534.
• 4. Orhan M, Taş Tuna A, Ünal Y, Arslan M, Yazar H, Sezen ŞC, Gözükara SI, Palabıyık O. The effects of amantadine on lung tissue in lower limb ischemia/reperfusion injury model in rats. Turk Gogus Kalp Damar Cerrahisi Derg 2021;29:77-83.
• 5. Kirisci M, Oktar GL, Ozogul C, Oyar EO, Akyol SN, Demirtas CY, Arslan M. Effects of adrenomedullin and vascular endothelial growth factor on ischemia/reperfusion injury in skeletal muscle in rats. J Surg Res 2013;185:56-63.
• 6. Koksel O, Yildirim C, Cinel L, Tamer L, Ozdulger A, Bastürk M, Degirmenci U, Kanik A, Cinel I. Inhibition of poly (ADP-ribose) polymerase attenuates lung tissue damage after hind limb ischemia-reperfusion in rats. Pharmacol Res 2005;51:453-62.
• 7. de Resende MA, Pantoja AV, Barcellos BM, Reis EP, Consolo TD, Módolo RP, Domingues MA, Assad AR, Cavalcanti IL, Castiglia YM, Módolo NS. Ischemic Post conditioning and Subanesthetic S(+)-Ketamine Infusion: Effects on Renal Function and Histology in Rats. Biomed Res Int 2015;2015:864902.
• 8. Cámara-Lemarroy CR, Guzmán-de la Garza FJ, Alarcón-Galván G, Cordero-Pérez P, Fernández-Garza NE. Theeffects of NMDA receptor antagonists over intestinal ischemia/reperfusion injury in rats. Eur J Pharmacol 2009;621:78-85.
• 9. Hubsher G, Haider M, Okun MS. Amantadine: the journey from fighting flu to treating Parkinson disease. Neurology 2012;3;78:1096-9.
• 10. Tan L, Ge H, Tang J, Fu C, Duanmu W, Chen Y, Hu R, Sui J, Liu X, Feng H. Amantadine preserves dopamine level and attenuates depression-like behavior induced by traumatic brain injury in rats. Behav Brain Res 2015;279:274-82.
• 11. Fantini GA, Conte MS. Pulmonary failure following lower torso ischemia: clinical evidence for a remote effect of reperfusion injury. AmSurg 1995;61:316-9.
• 12. Halliwell B. Superoxide, iron, vascular endothelium and reperfusion injury. Free Radic Res Commun 1989;5:315-8.
• 13. Joyce M, Kelly CJ, Chen G, Bouchier-Hayes DJ. Pravastatin attenuates lower torso ischaemia-reperfusion-induced lung injury by upregulating constitutive endothelial nitricoxid esynthase. Eur J Vasc Endovasc Surg 2001;21:295-300.
• 14. Fakouri A, Asghari A, Akbari G, Mortazavi P. Effects of folic acid administration on testicular ischemia/reperfusion injury in rats. Acta Cir Bras 2017;32:755-766.
• 15. Kapan Ş, Kiriş İ, Kılbaş A, Altuntaş İ, Karahan N, Okutan H. The effect of erythropoietin on lung injury in rat aortic ischemia-reperfusion. Turkish J Thorac Cardiovasc Surg 2009;17:110-116.
• 16. Sakamaki F, Hoffmann H, Müller C, Dienemann H, Messmer K, Schildberg FW. Reduced lipid peroxidation and ischemia-reperfusion injury after lung transplantation using low-potassiumdextran solution for lung preservation. Am J Respir Crit Care Med 1997;156(4 Pt 1):1073-81.
• 17. Pehlivan M, Hazinedaroglu SM, Kayaoglu HA, Erkek AB, Keklik T, Canbolat O, Kocak S. The effect of diosmin hesperidin on intestinal ischaemia—reperfusion injury. Acta Chir Belg 2004;104:715-8.
• 18. İsbir S, Akgün S, Ak K, Zeybek Ü, Ayd›n M, Civelek A, Tekeli A, Çobanoğlu A. Akut alt ekstremite iskemi reperfüzyon hasarının akciğer serbest oksijen radikalleri üzerine olan etkisi. TGKDCD 2000; 8: 2,629-31.
• 19. Önem G, Saçar M, Aybek H, Kocamaz E, Adalı F, Saçkan Gökhan K, et al. Protective effects of cilostazol and levosimendan on lung injury induced by lower limb ischemia-reperfusion. Turk Gogus Kalp Damar 2012;20:577-583.
• 20. Koksel O, Ozdulger A, Tamer L, Cinel L, Ercil M, Degirmenci U, Unlu S, Kanik A. Effects of caffeicacidphenethyl ester on lipopolysaccharide-induced lung injury in rats. Pulm Pharmacol Ther 2006;19:90-5.
• 21. Küçükebe ÖB, Özzeybek D, Abdullayev R, Ustaoğlu A, Tekmen I, Küme T. Effect of dexmedetomidine on acute lung injury in experimental ischemia-reperfusion model. Braz J Anesthesiol 2017;67:139-146.