Local Administration of Adenosine and Adenosine A1 Receptor Agonist CPA Protects Against Intestinal Ischemia-Reperfusion Injury in Rats

Yıl 2009, Cilt: 14 Sayı: 4, 231 - 236, 01.08.2009

Veysel Haktan Özaçmak Hale Sayan

Öz

Objective: Adenosine and adenosine A1 receptor (A1AR) agonists have potential protective effects against reperfusion injury in variety of tissues. The purpose of the present study was to investigate possible effects of topical administration of adenosine and A1AR agonist on reperfusion-induced small intestinal injury in rat. Materials and Methods: Rats were randomized to five groups each including six as following: sham-operated control; ischemia-reperfusion (I/R) control; adenosine + I/R; A1AR agonist 2-chloro-N6-cyclopentyladenosine (CPA) + I/R; and A1AR antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) + adenosine + I/R. Following topical administration of the drugs into abdominal cavity for 5 min, intestinal I/R was established by clamping superior mesenteric artery (SMA) for 30 minutes followed by 180 min of reperfusion period. Afterwards terminal ileum samples were collected and immediately transferred to isolated organ bath for measuring contractile response to carbachol. Furthermore, additional tissue samples were harvested for measuring the levels of malondialdehyde (MDA) and reduced glutathione (GSH). Results: I/R significantly increased lipid peroxidation while decreasing the GSH. Contractile responses were seriously reduced in I/R group compared to that of the sham control group. Pretreatment with adenosine or CPA not only decreased lipid peroxidation but also ameliorated contractile response and GSH levels remarkably. These beneficial effects were abolished by pretreatment with A1AR antagonist DPCPX. Conclusion: Evidences we collected suggest that besides systemic administration, local application of adenosine and A1AR agonist CPA also attenuate ischemic intestinal injury via, at least, decreasing oxidative stress and enhancing antioxidant defense.

Anahtar Kelimeler

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Adenozin ve Adenozin A1 Reseptör Agonisti CPA'nın Lokal Uygulanımı Sıçan İnce Barsak Hasarına Karsı Koruyucu Etkiler Göstermektedir

Öz

Amaç: Adenozin ve A1 adenozin reseptör (A1AR) agonistleri, çeşitli dokuların reperfüzyon hasarına karşı koruyucu etkilere sahiptir. Çalışmanın amacı, sıçan ince barsağının reperfüzyon harabiyetinde adenozin ve A1AR agonistinin lokal uygulanmasının etkilerini incelemekti. Gereç ve Yöntemler: Sıçanlar herbiri altı hayvan içeren beş gruba rastgele olarak aşağıdaki gibi ayrıldı: sham kontrol; iskemi-reperfüzyon (I/R) kontrol; adenozin + I/R; A1AR agonisti 2-kloro-N6-siklopentiladenozin (CPA) + I/R ve A1AR antagonisti 8-siklopentil-1,3-dipropilksantin (DPCPX) + adenozin + I/R. Đlaçların abdominal boşluğa 5 dk boyunca lokal uygulanmasını takiben barsak I/R’u, süperiyor mezenter arterin 30 dk klempe edilmesi ve sonrasındaki 180 dk lık reperfüzyon dönemi ile sağlandı. Daha sonra terminal ileum örnekleri toplandı ve karbakole olan kasılma yanıtlarını ölçmek için hızlıca izole organ banyosuna alındı. Ayrıca malondialdehid (MDA) ve indirgenmiş glutatyon (GSH) düzeylerini ölçmek için de ek doku örnekleri alındı. Bulgular: I/R, lipid peroksidasyonunu ileri düzeyde yükseltirken, indirgenmiş glutatyonu düşürdü. Sham kontrol grubuyla karşılaştırıldığında, kasılma yanıtları I/R grubunda ciddi düzeyde azaldı. Adenozin veya CPA ön tedavisi, sadece lipit peroksidasyonunu azaltmakla kalmadı aynı zamanda kasılma yanıtı ve GSH düzeyini de ileri derecede iyileştirdi. Bu yararlı etkilerin, A1AR anatgonisti DPCPX ön tedavisi ile ortadan kalktığı gözlendi. Sonuç: Elde ettiğimiz kanıtlar, sistemik uygulanımının yanı sıra, adenozin ve A1AR agonisti CPA’nın lokal uygulanmasının da iskemik barsak harabiyetini, en azından oksidatif stresi azaltarak ve antioksidan savunmayı güçlendirerek iyileştirdiğini önermektedir.

Anahtar Kelimeler

Adenozin, adenozin A1 reseptörü, barsak iskemi/reperfüzyonu

Kaynakça

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