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.