Prevention of lung injury by iloprost following hind limb ischemia and reperfuison model in rats

Yıl 2018, , 76 - 80, 25.06.2018

Atike Tekeli Kunt , Selim İsbir Ali Civelek Serdar Akgun Arzu Ergen Ozlem Yapicier Aydin Sav Sinan Arsan

https://doi.org/10.18663/tjcl.396679

Öz

Aim: The major part of tissue damage
occurs upon reperfusion and is mediated by activated neutrophils that release
oxygen free radicals. Following hind-limb ischemia/reperfusion, lung injury due
to neutrophil infiltration and oxygen free radicals has been demonstrated.
Previous studies have shown that this injury can be prevented
pharmacologically. Iloprost is a long acting stable analog of prostacyclin. The
aim of this study is to test the effect of iloprost in prevention of lung
injury due to lower limb ischemia/reperfusion.

Material and Methods: Through a midline
laparotomy infrarenal abdominal aorta was approached and cross-clamped in 20
male Spraque-Dawley rats for 2 hours. At the time of declamping Group I animals
(n=8) received iloprost (0,1µg/kg/min) and Group II animals (n=8) received
normal saline (0,1ml/kg/min) continously for 4 hours. Third group was the sham
group (n=4). The lung tissue assays were performed for measurement of lipid
peroxidation end product malondealdehyde and also total glutathione. Lung
tissues were also examined histopathologically under light microscopy.

Results: The malondealdehyde levels in
the iloprost group were significantly lower than the control group (p<0,05).
The glutathione levels did not show any difference between the iloprost and the
control groups (p>0,05). Histopathological examination revealed that the
structure of the lung tissue was preserved in the iloprost group whereas lung
tissue of the control group had evidence of injury.

Conclusion: Our results suggest that
iloprost reduces the production of oxygen free radicals and prevents lung
injury due to lower limb ischemia reperfusion.

Anahtar Kelimeler

ischemia, reperfusion, iloprost

Sıçanlarda alt ekstremite iskemi reperfüzyon hasarını takiben gelişen akciğer hasarının iloprost ile önlenmesi

Öz

Amaç:  İskemi ve bunu takip
eden reperfüzyon dönemi sonrasında ortaya çıkan doku hasarı

büyük ölçüde reperfüzyon sırasında
gerçekleşir. Aktive olmuş nötrofillerden salınan serbest

oksijen radikalleri bu hasarda
önemli rol oynarlar. Alt ekstremite iskemi-reperfüzyonu

sonrasında görülen akciğer
hasarında nötrofil infiltrasyonunun ve serbest oksijen

radikallerinin önemi
gösterilmiştir. Bu hasarı farmakolojik olarak önlemek için birçok çalışma

yapılmıştır. İloprost, uzun etkili
bir prostasiklin analoğudur. Çalışmanın amacı, alt ekstremite

iskemi reperfüzyonu sonrası ortaya
çıkan akciğer hasarını önlemedeki iloprostun etkisini

araştırmaktır.

Gereç ve Yöntemler: Çalışmada 20 adet Spraque-Dawley cinsi erkek
sıçan kullanıldı. Orta hattan

yapılan laparotomi ile abdominal aortaya
ulaşıldı. Grup I (n=8) ve Grup II (n=8) de bulunan

deneklerin infrarenal aortalarına 2
saat boyunca kross klemp uygulandı. Klemp kaldırıldığı

sırada Grup I’de bulunan deneklere
0,1 g/kg/dk dozunda iloprost ve Grup II’de bulunan

deneklere 0,1ml/kg/dk serum
fizyolojik sürekli infüzyon şeklinde 4 saat boyunca verildi. Grup

III(n=4) sham grubu olarak
belirlendi. Denekler 4. saatin sonunda sakrifiye edilerek akciğer

dokuları çıkarıldıve biyokimyasal
ve histopatolojik inceleme yapıldı.

Bulgular: İloprost verilen grupta malondealdehyde seviyeleri
kontrol grubuna göre

istatistiksel olarak anlamlı
derecede düşük bulundu (p<0.05). Glutatyon düzeylerinde ise

kontrol ve iloprost grupları
arasında anlamlı fark bulunmadı (p>0.05). Histopatolojik

incelemede, iloprost verilen grupta
akciğer dokusunun korunmuş olduğu gözlenirken kontrol

grubunda akciğer doku harabiyeti
tespit edilmiştir.

Sonuç: Sonuçlarımız alt ekstremite iskemi-reperfüzyonu sonrasında
ortaya çıkan akciğer

hasarının önlenmesinde iloprostun
serbest oksijen radikal oluşumunu azaltarak etkili

olduğunu göstermektedir.

Anahtar Kelimeler

iloprost, iskemi, reperfüzyon, iloprost

Kaynakça

• 1. Klausner JM, Paterson IS, Valeri R, Hechtman HB. Limb ischemia induced increase in permeability is mediated by leukocytes and leukotrienes. Ann Surg 1988; 208: 755-60.
• 2. Klausner JM, Paterson IS, Kozbik L, Valeri R, Shepro D, Hetchtman HB. Oxygen free radicals mediate ischemia-induced lung injury. Surgery 1989; 105: 192-99.
• 3. Gyurkovics E, Aranyi P, Stagnl R et al. Postconditioning of the lower limb protection against reperfusion syndrome. J Surg Res 2011; 169: 139- 47.
• 4. Akgun S, Tekeli A, Isbir SC et al. FK506 to prevent lung injury after hindlimb ischemia and reperfusion in a rat model: an electron microscopic study. Surg Today 2004; 34: 678-84.
• 5. Groeneveld AB, Raijmakers PG, Rauwerda JA, Hack CE. The inflammatory response to vascular surgery associated ischemia and reperfusion in man:effect of postoperative pulmonary function. Eur J Endovasc Surg 1997; 14: 351-59.
• 6. Gaines GC, Welborn MB, Moldawer LL, Huber TS, Harward TR, Seeger JM. Attenuation of skeletal muscle ischemia-reperfusion by tumor necrosis factor. J Vasc Surg 1999; 29: 370-76.
• 7. Bengisun U, Köksoy C, Bengisun JS, Bayraktaroglu G, Camur A, Aras N. Ischemia and reperfusion of pulmonary hypertension and leukosequestration following lower limb ischemia. Prost Leuko Essen Fatty Acids 1997; 56: 117-20.
• 8. İsbir CS, Akgün S, Ak K et al. Akut alt ekstremite iskemi/reperfüzyon hasarının akciğer serbest oksijen radikalleri üzerine olan etkisi. TGKDCD 2000; 8: 629-31.
• 9. Rocker MG. Ischemia/reperfusion, inflammatory responses and acute lung injury. Thorax 1997; 52: 841-42.
• 10. Raijmakers PGHM, Groeneveld ABJ, Rauwerda JA, Teule GJJ, Hack CE. Acute lung injury after aortic surger: the relation between lung and leg microvascular permeability to indium-labelled transferrin and circulating mediators. Thorax 1997; 52: 866-71.
• 11. Grant SM, Goa KL. Iloprost. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in peripheral vascular disease, myocardial ischaemia and extracorporeal circulation procedures. Drugs 1992; 43: 889-924.
• 12. Wang L, Jin YZ, Zhao QH et al. Hemodynamic and gas exchange effects of inhaled iloprost in patients with COPD and pulmonary hypertension. Int J Chron Obstruct Pulmon Dis. 2017; 12: 3353-60.
• 13. Pantazi E, Bejaoui M, Folch-Puy E, Adam R, Roselló-Catafau J. Advances in treatment strategies for ischemia reperfusion injury. Expert Opin Pharmacother. 2016; 17: 169-79.
• 14. Bhattacharyya, A., Chattopadhyay, R., Mitra, S., Crowe, S.E., Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol. Rev. 2014; 94: 329–54.
• 15. Messent M, Griffiths MJD, Evans TW. Pulmonary vascular reactivity and ischemia reperfusion injury in the rat. Clin Sci 1993; 85: 71–75.
• 16. M. Sacar, V. Ozcan, H. Aybek et al., Vitamin C and iloprost attenuate skeletal muscle injury caused by ischemia-reperfusion of the lower extremities. TGKDCD 2005;13: 374–8.
• 17. Aytacoglu BN, Sucu N, Tamer L et al., Iloprost for the attenuation of ischaemia/reperfusion injury in a distant organ. Cell Biochem Func 2006; 24: 341–46.
• 18. Tiryakioglu O, Erkoc K, Tunerir B, Uysal O, Altin HF, Gunes T, Aydin S. The effect of iloprost and N-acetylcysteine on skeletal muscle injury in an acute aortic ischemia-reperfusion model: an experimental study. Biomed Res Int. 2015; 2015: 453748.