Rat Alt Ekstremite İskemi Reperfüzyon Hasarının Tenoksikam ile Önlenmesi

Öz

Amaç: Alt ekstremitede uzun süren iskemi/reperfüzyon İ/R lokal dokuda belirgin kas hasarına neden olur. Bu çalışmada alt ekstremite İ/R modelinde bir COX-2 inhibitörü olan tenoksikamın antioksidan etkinliğini araştırmak amaçlanmıştır.Gereç ve Yöntemler: Erkek Wistar ratlarda anestezi verilmesini takiben sol alt ekstremiteye 3 saat iskemi ve 24 saat reperfüzyon uygulandı. Çalışmaya, her birinde 7 denek bulunan 4 grup dâhil edildi. Denekler Grup 1 Kontrol , Grup 2 İ/R, Sham , Grup 3 İ/R, 2,5 mg/kg Tenoksikam ve Grup 4 İ/R, 10 mg/kg Tenoksikam gruplarına ayrıldı. Tenoksikam 3 saat’lik iskeminin ardından hemen intraperitoneal olarak uygulandı. 24 saatlik reperfüzyon dönemi sonunda gastroknemius kasından örnekler alınarak, elektron mikroskopunda incelendi.Bulgular: Elektron mikroskopi ile yapılan çalışmada Grup 2’de, Grup 1’e göre belirgin doku hasarı tespit edildi p=0,005 . Grup 2ʼde yoğun lökosit infiltrasyonu, nekroz, ödem, sarkoplazmik retikulum dilatasyonu, mitokondri kristalarında silinme, miyofibril dezorganizasyonu gözlendi. Grup 3 ve Grup 4ʼde, Grup 2’ye kıyasla özellikle sarkoplazmik retikulum dilatasyonu, mitokondri kristalarında silinme ve miyofibril dezorganizasyonu anlamlı olarak düşük bulundu Sırasıyla p=0,007 ve p=0,006 . Grup 3 ve Grup 4ʼde daha az histopatolojik etkilenme oldu. Tenoksikamın, doza bağlı olarak histolojik değişiklikleri önlediği gözlendi.Sonuç: Alt ekstremite İ/R hasarında belirgin histopatolojik değişiklikler ortaya çıkar. Tenoksikamın kas dokusu iskemi-reperfüzyon hasarını önlemede koruyucu bir etkisi olduğu görülmektedir

Anahtar Kelimeler

• İskemi reperfüzyon, Tenoksikam, Alt ekstremite, Rat, Histopatoloji

Prevention of Rat Lower Extremity Ischemia Reperfusion Injury With Tenoxicam

Abstract

Objective: Prolonged ischemia / reperfusion I/R in the lower extremity causes significant muscle damage to the local tissue. In this study, it was aimed to investigate the antioxidant activity of tenoxicam, a COX-2 inhibitor, in rat lower extremity I/R model.Material and Methods: Following anesthesia, 3-hour ischemia and 24-hour reperfusion were applied to the left lower extremity in male Wistar rats. The study included 4 groups, each with 7 subjects. Subjects were divided into Group 1 Control , Group 2 I/R, Sham , Group 3 I/R, 2.5 mg/kg Tenoxicam , and Group 4 I/R, 10 mg/kg Tenoxicam . Tenoxicam was administered intraperitoneally immediately after 3 hours of ischemia. At the end of the 24-hour reperfusion period, samples were taken from the gastrocnemius muscle and examined under an electron microscope.Results: In the study performed with electron microscopy, significant tissue damage was detected in Group 2 compared to Group 1 p=0.005 . In Group 2, intense leukocyte infiltration, necrosis, edema, dilatation of sarcoplasmic reticulum, loss of mitochondrial crystals, and myofibril disorganization were observed. In Group 3 and Group 4, sarcoplasmic reticulum dilatation, disappearance of cristae mitochondria, and myofibril disorganization were significantly lower than in Group 2 p=0.007 and p=0.006, respectively . There was less histopathological involvement in Group 3 and Group 4. Tenoxicam was observed to prevent dose-dependent histological changes.Conclusion: Significant histopathological changes occur in lower extremity I/R injury. Tenoxicam appears to have a protective effect in preventing muscle tissue ischemia-reperfusion injury

Keywords

• Ischemia-reperfusion, Tenoxicam, Lower extremity, Rat, Histopathology

References

1. Alizan A, Khalil C, Farah A, John C. Reperfusion injury. Plast. Reconstr Surg 2006; 117: 1024-33.
2. Korthuıs R J, Grisham M B. Leukocyte depletion attenuates vasculer injury in postischemic skeletal muscle. Am J Physiol 1988; 254:823-7.
3. Dupouy V, Fere P, Uro-coste E. Time course of cox-1 and cox-2 expression during ischemia-reperfüsion in rat skeletal muscle. J Appl Physiol 2006; 100(1):233-9.
4. Galvao R, Diogenes J, Maia G. Tenoxicam exerts a neuroprotective action after cerebral ischemia in rats. Neurochem Res 2005; 30:39-46.
5. Patel N, Cuzzocrea S, Collino M. The role of cycloxygenase-2 in the rodent kidney following ischaemia/reperfusion injury in vivo. Eur J Pharmacol 2007; 562:148-54.
6. Nilsen OG. Clinical pharmacokinetics of tenoxicam. Clin Pharmacokinet 1994; 26:16-43.
7. Ichihara S, Tomisawa H, Fukazawa H, Tateishi M, Joly R, Heintz R. Oxidation of tenoxicam by leukocyte peroxidases and H2O2 produces novel products. Drug Metab Dispos 1989; 17:463-8.
8. Paino M, Ximenes V, Fonseca L. Effect of therapatic plasma concentrations of non-steroidal anti-inflammatory drugs on the production of reactive oxygen species by activated rat neutrophils. Braz J Med 0 Bio Res 2005; 38: 543-51.

9. Ezberci F, Bulbuloglu E, Ciragil P. Intraperitoneal tenoxicam to prevent abdominal adhesion formation in a rat peritonitis model. Surg Today 2006; 36:361-6.
10. Celebioglu B, Eslamboul N, Olcay E. The effect of tenoxicam on intraperitoneal adhesions and prostaglandin E2 levels in mice. Anesth Analg 1999; 88:939-42.
11. Mol Y. Rat alt ekstermite iskemi reperfüzyon modelinde tenoksikamın antioksidan etkinliğinin araştırılması (uzmanlık tezi). Dokuz Eylül Üniversitesi, Tıp Fakültesi, 2008.
12. Duru S, Koca U, Öztekin S, Olguner Ç, Elar Z. Antithrombin III pretreatment reduces neutrophil recruitment into the lung and skeletal muscle tissues in the rat model of biletaral lower limb and reperfusion: A Pilot Study. Acta Anaesthesiol Scand 2005; 49:1142-8.
13. Ozcan O, Erdal H, Yonden Z. İskemi-reperfüzyon hasarı ve oksidatif stres ilişkisine biyokimyasal bakış. Mustafa Kemal Üniv Tıp Derg 2015; 6(23):27-33.
14. Suleyman H, Gül V, Hirik E. İskemi-reperfüzyon hasarı. Erzincan Medical Journal 2018: 1(2):51-4.
15. Petrasek PF, Homer-Vanniasinkam S, Walker PM. Determinants of ischemic injury to skeletal muscle. J Vasc Surg 1994; 19:623-31.
16. Kumar V, Cotran R, Rabbins S. Temel Patoloji, 6. baskı. Çeviri: Kemal Kutlu, İstanbul: Nobel Yayınları, 2000: 4-24.
17. Skjeldal S, Torvik A, Grİgaard B, Nordsletten L, Lyberg T. Histological studies on postischemic rat skeletal muscles. With emphasis on the time of leukocyte invasion. Eur Surg Res 1993; 25:348-57.
18. Blaisdell F W. The pathophysiology of skeletal muscle ischemia and the reperfusion syndrome: A review. Cardiovasc Surg 2002; 10:620-30.
19. Sirsjö A, Gidlöf A, Nilsson G, Povlsen B. Skeletal muscle blood flow after prolonged tourniquet ischaemia and reperfusion with and without intervening reoxygenation: An experimental study in rats using laser Doppler perfusion imaging. Scand J Plast Reconstr Surg Hand Surg 1999; 33:281-5.
20. Edna M, Maeli D, Vitalino D. Ischaemia and reperfusion effects on skeletal muscle tissue: Morphological and histochemical studies. Int J Exp Path 2007; 88:147-54.
21. Duarte JA, Glöser S, Remião F, Carvalho F, Bastos ML, Soares JM, Appell HJ. Administration of tourniquet. I. Are edema and oxidative stress related to each other and to the duration of ischemia in reperfused skeletal muscle? Arch Orthop Trauma Surg 1997; 116:97-100.
22. Appell H J, Glöser S, Duarte JA, Zellner A, Soares JM. Skeletal muscle damage during tourniquet-induced ischaemia. The initial step towards atrophy after orthopaedic surgery? Eur J Appl Physiol Occup Physiol 1993; 67:342-7.
23. Appell HJ, Glöser S, Soares J, Duarte JA. Structural alterations of skeletal muscle induced by ischemia and reperfusion. Basic Appl Myol 1999; 9:263-8.