Ali Baran BUDAK, Kemal KORKMAZ, Hikmet Selçuk GEDİK, Gökhan LAFÇI, Ertuğrul KAYA, HANDAN ANKARALI, Serdar GÜNAYDIN

Montelukastın karaciğer ve böbrekteki iskemi/reperfüzyon hasarına olan etkisi

Amaç: Torakoabdominal aort anevrizması cerrahisinin sebep olabildiği splanknik iskemi, karaciğer ve/veya böbrek hasarının neden olduğu ciddi postoperatif komplikasyonlarla sonuçlanabilir. Bu çalışmada seçici tersinir bir CysLT1 reseptör antagonisti olan montelukastın, aortanın geçici oklüzyonuyla yaratılan böbrek ve karaciğer iskemi-reperfüzyon (I/R) hasarı üzerindeki koruyucu etkisini incelemek için tasarlandı. Gereç ve Yöntemler: Yirmi bir erkek Sprague-Dawley tipi sıçan, rasgele üç gruba (her grupta n=7) ayrıldı; G1 (aort oklüzyonu ve montelukast uygulaması yok), G2 (45 dakika aort oklüzyonu; montelukast uygulması yok) ve G3 (45 dakika aort oklüzyonu, 10 mg/kg montelukast uygulaması). Reperfüzyonun 48. saatinde böbrek ve karaciğerden alınan doku örneklerinden histopatolojik değerlendirme ve HSP 70, interlökin-6 ve miyeloperoksidaz (MPO) ile immünohistokimyasal boyama yapıldı. Bulgular: Böbrekten alınan doku örnekleri tübüler hücre dejenerasyonu, sitoplazmik vakuol formasyonu, hemoraji ve tübüler dilatasyon açısındna incelendi ve gruplar arasında istatistiksel olarak anlamlı fark bulundu (P = 0.001, P = 0.017, P = 0.001). G1 ve G3 gruplarında HSP-70 ile boyanmada G2 ye göre anlamlı fark saptandı (P = 0.001). G3 karaciğer örneklerinde hepatosit dejenerasyonu G1 ve G2 den anlamlı olarak düşüktü (P = 0.027). Sonuçlar: Yapılan çalışmanın bulguları, montelukastın böbrek ve karaciğer üzerinde koruyucu etkileri olduğunu histopatolojik ve immünohistokimyasal olarak göstermiştir. Montelukastın koruyucu etkileri, ilacın antioksidan ve antiinflamatuar etkilerine bağlanabilir.

Anahtar Kelimeler:

İskemi-reperfüzyon injurisi, montelukast, böbrek, karaciğer

Effect of montelukast on hepatic and renal ischemia/reperfusion injury

Aim: The thoracoabdominal aortic aneurysm surgery may cause splanchnic ischemia and may result in severe postoperative complications caused by liver and/or kidney injury. This study investigated the effect of temporary occlusion of the aorta on the development of I/R injury of liver and kidney and the protective effect of montelukast, a selective reverse CysLT1 receptor antagosit. Material and Methods: Twenty-one male Sprague-Dawley rats were randomly assigned to three groups (n=7 per group) as G1 (no aortic occlusion and montelukast administration), G2 (45 min. aortic occlusion; no montelukast administration) and G3 (45 min. aortic occlusion, 10 mg/kg montelukast administration). At the 48th hour of reperfusion, kidney and liver samples were dissected for histopathological evaluation and immunohistochemical staining for HSP70, interleukin-6 and myeloperoxidase (MPO). Results: Tissue samples taken from the kidney showed significant intergroup differences in terms of tubular cell degeneration, cytoplasmic vacuole formation, hemorrhage and tubular dilatation (P = 0.001, P = 0.017, P = 0.001, P = 0.001 respectively). There was a significant difference with regards to HSP-70 stain (P = 0.01) in favor of G1 and G3 with respect to G2. Hepatocyte degeneration in the liver samples of G3 was significantly lower than that of G1 and G2 (P = 0.027). Conclusion: The findings of the current study demonstrated that montelukast has protective effects on both kidney and liver; and were confirmed histopathologically and immunohistochemically. The protective effects of montelukast can be attributed to its potential of anti-oxidative and anti-inflammatory actions.

Keywords:

Ischemia-reperfusion injury, montelukast, kidney, liver,

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