Mustafa ORHAN, Ayça Taş TUNA, Yusuf ÜNAL, Mustafa ARSLAN, hayrullah yazar, Şaban Cem SEZEN, Sezen Irmak GÖZÜKARA, Onur PALABIYIK

The effects of amantadine on lung tissue in lower limb ischemia/reperfusion injury model in rats

tissue of after lower limb ischemia/reperfusion injury in rats. Methods: A total of 24 Wistar rats were divided into four equal groups including six rats in each: sham group (Group S), amantadine group (Group A), ischemia/reperfusion group (Group I/R), and ischemia/reperfusion + amantadine group (Group I/R-A). All groups underwent a midline abdominal incision. In Groups I/R and I/R-A, the infrarenal abdominal aorta was clamped for 120 min and, then, reperfused for 120 min after removal of the clamp. Amantadine hydrochloride 45 mg/kg was administered intraperitoneally to the rats of Groups A and Group I/R-A 15 min before surgery. At the end of reperfusion period (240 min), all rats were sacrificed, and their lung tissues were obtained. Lung tissue catalase and superoxide dismutase activities and glutathione S-transferase and malondialdehyde levels were analyzed. Lung tissues were examined histopathologically. Results: Catalase activity was lower in Groups A, I/R, and I/R-A compared to Group S. Superoxide dismutase activity was higher in Group I/R than Group S. Superoxide dismutase activity in Groups I/R-A and A decreased, compared to Groups S and I/R. Glutathione S-transferase levels decreased in Groups I/R and A, compared to Group S. Glutathione S-transferase levels in Group I/R-A were higher than Groups I/R and A. The highest level of malondialdehyde was found in Group I/R and the lowest level was found in Group I/R-A. According to histopathological examination, infiltration scores were significantly lower in Group S than Groups I/R and I/R-A (p=0.009 and p=0.011, respectively). The alveolar wall thickening scores in Group I/R were also significantly higher than Groups S and Group A (p=0.001 and p=0.001, respectively). Conclusion: Lung tissue can be affected histopathologically by ischemia/ reperfusion injury and this injury can be reversed by amantadine administration.

Amantadinin alt ekstremite iskemi/reperfüzyon sıçan modelinde akciğer dokusu üzerindeki etkileri

Amaç: Bu çalışmada, sıçanlarda alt ekstremite iskemi/reperfüzyon hasarından sonra amantadinin akciğer dokusu üzerindeki etkisi araştırıldı. Çalışma planı: Toplam 24 adet Wistar cinsi sıçan her grupta altı sıçan olacak şekilde dört eşit gruba ayrıldı: Sham grubu (Grup S), amantadin grubu (Grup A), iskemi/reperfüzyon grubu (Grup I/R) ve I/R+amantadin grubu (Grup I/R-A). Tüm gruplara orta abdominal insizyon uygulandı. Grup I/R ve I/R-Aʼda infrarenal abdominal aorta 120 dk. süreyle klemplendi ve ardından klemp kaldırılarak 120 dk. süreyle reperfüze edildi. Grup A ve I/R-Aʼdaki sıçanlara 45 mg/kg amantadin hidroklorür cerrahiden 15 dk. önce intraperitoneal olarak uygulandı. Reperfüzyon periyodu sonunda (240 dk.) tüm sıçanlar sakrifiye edildi ve akciğer dokuları alındı. Akciğer dokusunda katalaz ve süperoksit dismutaz aktiviteleri ve glutatyon S-transferaz ve malondialdehit düzeyleri çalışıldı. Akciğer dokuları histopatolojik olarak incelendi. Bulgular: Katalaz aktivitesi Grup A, I/R ve I/R-Aʼda, Grup S’ye kıyasla daha düşüktü. Süperoksit dismutaz aktivitesi Grup I/Rʼde, Grup Sʼye kıyasla daha yüksekti. Grup I/R-A ve Aʼda, Grup S ve I/Rʼye kıyasla, süperoksit dismutaz aktivitesi azaldı. Glutatyon S-transferaz düzeyleri Grup I/R ve Aʼda, Grup S’ye kıyasla azaldı. Glutatyon S-transferaz düzeyleri, Grup I/RA’da, Grup I/R ve A’ya kıyasla daha yüksekti. Malondialdehit düzeyleri, Grup I/R’de en yüksek ve Grup IR-Aʼda en düşük izlendi. Histopatolojik incelemeye göre, Grup Sʼde infiltrasyon skoru Grup I/R ve Grup I/R-Aʼya kıyasla, anlamlı düzeyde daha düşüktü (sırasıyla. p=0.009 ve p=0.011). Grup I/Rʼde alveol duvar kalınlaşması skoru, Grup S ve Grup Aʼya kıyasla, anlamlı düzeyde yüksekti (sırasıyla, p=0.001 ve p=0.001). Sonuç: Akciğer dokusu iskemi/reperfüzyon hasarından etkilenebilir ve bu hasar amantadin kullanımı ile geri döndürülebilir.

PDF

___

1. Jennings RB, Reimer KA. The cell biology of acute myocardial ischemia. Annu Rev Med 1991;42:225-46. 2. Zimmerman BJ, Granger DN. Reperfusion injury. Surg Clin North Am 1992;72:65-83.
3. Dammers R, Wehrens XH, oude Egbrink MG, Slaaf DW, Kurvers HA, Ramsay G. Microcirculatory effects of experimental acute limb ischaemia-reperfusion. Br J Surg 2001;88:816-24.
4. Khalil AA, Aziz FA, Hall JC. Reperfusion injury. Plast Reconstr Surg 2006;117:1024-33.
5. Takito AM, Silva JCCB , Bueno V, Franco M, Burihan E. Ischemic and reperfusion syndrome of hind limbs: functional and histological renal changes in rats. Medicina (Ribeirão Preto) 2005;38:294-300.
6. Duru S, Koca U, Oztekin S, Olguner C, Kar A, Coker C, et al. Antithrombin III pretreatment reduces neutrophil recruitment into the lung and skeletal muscle tissues in the rat model of bilateral lower limb ischemia and reperfusion: a pilot study. Acta Anaesthesiol Scand 2005;49:1142-8.
7. Fantini GA, Conte MS. Pulmonary failure following lower torso ischemia: clinical evidence for a remote effect of reperfusion injury. Am Surg 1995;61:316-9.
8. İşbir S, Akgün S, Ak K, Civelek A, Tekeli A, Çobanoğlu A, et al. Effect of acute lower limb ischemia/reperfusion injury on the free oxygen radical systems in lungs. Turk Gogus Kalp Dama 2000;8:632-4.
9. Baltalarli A, Önem G, Gökşin İ, Rendeci O, Saçar M, Çolakoğlu N. Ischemic preconditioning increases the lung injury caused by ischemia. Turk Gogus Kalp Dama 2000;8:537-40.
10. Danysz W, Parsons CG, Kornhuber J, Schmidt WJ, Quack G. Aminoadamantanes as NMDA receptor antagonists and antiparkinsonian agents--preclinical studies. Neurosci Biobehav Rev 1997;21:455-68.
11. Farnebo LO, Fuxe K, Goldstein M, Hamberger B, Ungerstedt U. Dopamine and noradrenaline releasing action of amantadine in the central and peripheral nervous system: a possible mode of action in Parkinson's disease. Eur J Pharmacol 1971;16:27-38.
12. Cámara-Lemarroy CR, Guzmán-de la Garza FJ, Alarcón- Galván G, Cordero-Pérez P, Fernández-Garza NE. The effects of NMDA receptor antagonists over intestinal ischemia/ reperfusion injury in rats. Eur J Pharmacol 2009;621:78-85.
13. Özdemir HH, Demir CF, Berilgen MS, Akgün B, Kuloğlu T, Kapan O, et al. Protective effects of memantine induced by cerebral ischemia and reperfusion injury in rats. Turk J Neurol 2013;19:85-9.
14. Ozsüer H, Görgülü A, Kiriş T, Cobanoğlu S. The effects of memantine on lipid peroxidation following closed-head trauma in rats. Neurosurg Rev 2005;28:143-7.
15. Kirisci M, Oktar GL, Ozogul C, Oyar EO, Akyol SN, Demirtas CY, et al. Effects of adrenomedullin and vascular endothelial growth factor on ischemia/reperfusion injury in skeletal muscle in rats. J Surg Res 2013;185:56-63.
16. Koksel O, Yildirim C, Cinel L, Tamer L, Ozdulger A, Bastürk M, et al. Inhibition of poly(ADP-ribose) polymerase attenuates lung tissue damage after hind limb ischemiareperfusion in rats. Pharmacol Res 2005;51:453-62.
17. Yang CL, Chen CH, Tsai PS, Wang TY, Huang CJ. Protective effects of dexmedetomidine-ketamine combination against ventilator-induced lung injury in endotoxemia rats. J Surg Res 2011;167:e273-81.
18. Wang XD, Lu YL, Lai RC, Li YP, Huang W, Xu M. Protective effect of ketamine against acute rat lung injury induced by liopolysaccharide and its mechanism. Nan Fang Yi Ke Da Xue Xue Bao 2007;27:1848-50.
19. Xiao X, Zhang H, Wang H, Li Q, Zhang T. Neuroprotective effect of amantadine on corticosterone-induced abnormal glutamatergic synaptic transmission of CA3-CA1 pathway in rat’s hippocampal slices. Synapse 2017;71.
20. Giacino JT, Whyte J, Bagiella E, Kalmar K, Childs N, Khademi A, et al. Placebo-controlled trial of amantadine for severe traumatic brain injury. N Engl J Med 2012;366:819-26.
21. Tan L, Ge H, Tang J, Fu C, Duanmu W, Chen Y, et al. Amantadine preserves dopamine level and attenuates depression-like behavior induced by traumatic brain injury in rats. Behav Brain Res 2015;279:274-82.
22. Atahan E, Ergün Y, Kurutaş EB, Alici T. Protective effect of zinc aspartate on long-term ischemia-reperfusion injury in rat skeletal muscle. Biol Trace Elem Res 2010;137:206-15.
23. Kiriş İ, Okutan H, Savaş Ç, Yönden Z, Delibaş N. Deneysel aortik iskemi-reperfüzyon modelinde renal hasara gadolinyum klorürün etkisi. Damar Cerrahisi Dergisi 2005;14:13-8.
24. Kapan Ş, Kiriş İ, Kılbaş A, Altuntaş İ, Karahan N, Okutan H. Eritropoietinin sıçan aortik iskemi-reperfüzyonunda akciğer hasarı üzerine etkisi. Turk Gogus Kalp Dama 2009;17:110-6.
25. Reiter RJ, Melchiorri D, Sewerynek E, Poeggeler B, Barlow- Walden L, Chuang J, et al. A review of the evidence supporting melatonin’s role as an antioxidant. J Pineal Res 1995;18:1-11.
26. El-Sayyad SM, Soubh AA, Awad AS, El-Abhar HS. Mangiferin protects against intestinal ischemia/ reperfusion-induced liver injury: Involvement of PPAR-γ, GSK-3β and Wnt/β-catenin pathway. Eur J Pharmacol 2017;809:80-6.
27. Cavdar Z, Ural C, Celik A, Arslan S, Terzioglu G, Ozbal S, et al. Protective effects of taurine against renal ischemia/ reperfusion injury in rats by inhibition of gelatinases, MMP-2 and MMP-9, and p38 mitogen-activated protein kinase signaling. Biotech Histochem 2017;92:524-35.
28. Xia F, Xia Y, Chen S, Chen L, Zhu W, Chen Y, et al. Lipid emulsion mitigates impaired pulmonary function induced by limb I/R in rats through attenuation of local cellular injury and the subsequent systemic inflammatory response/ inflammation. BMC Anesthesiol 2017;17:83.
29. Zhang Y, Rong S, Feng Y, Zhao L, Hong J, Wang R, et al. Simvastatin attenuates renal ischemia/reperfusion injury from oxidative stress via targeting Nrf2/HO-1 pathway. Exp Ther Med 2017;14:4460-6.
30. Gutteridge JM. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem 1995;41:1819-28.
31. Uysal A, Burma O, Akar İ, Özsin Kaan K, Rahman A, Üstündağ B, et al. Protective effect of melatonin on lung injury caused by ischemia-reperfusion of the lower extremities. Turk Gogus Kalp Dama 2006;14:308-14.
32. Alaçam B, Ek RO, Yıldız Y, Serter M, Boylu NT, Temoçin S. Abdominalaorta iskemi- reperfüzyonuna bağlı gelişen akciğer hasarında karnozinin etkisi. Adnan Menderes Üniversitesi Tıp Fakültesi Dergisi 2010;11:41-7.
33. 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 Dama 2012;20:577-83.
34. Pararajasingam R, Nicholson ML, Bell PR, Sayers RD. Noncardiogenic pulmonary oedema in vascular surgery. Eur J Vasc Endovasc Surg 1999;17:93-105.
35. Carden D, Xiao F, Moak C, Willis BH, Robinson-Jackson S, Alexander S. Neutrophil elastase promotes lung microvascular injury and proteolysis of endothelial cadherins. Am J Physiol 1998;275:H385-92.
36. Windsor AC, Mullen PG, Fowler AA, Sugerman HJ. Role of the neutrophil in adult respiratory distress syndrome. Br J Surg 1993;80:10-7.
37. Akahane HGK, Gomes RZ, Paludo KS, Linhares F, Lopes L. The influence of allopurinol and post-conditioning on lung injuries induced by lower-limb ischemia and reperfusion in Wistar rats. Acta Cir Bras 2017;32:746-54.
38. 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;67:139-46.