Recovery of ischaemic injured porcine ileum: evidence for a contributory role of COM-1 and COX-2

Background: We have previously shown that the non-selective cyclooxygenase (COX) inhibitor indomethacin retards recovery of intestinal barrier function in ischaemic injured porcine ileum. However, the relative role of COX-1 and COX-2 elaborated prostaglandins in this process is unclear. Aims: To assess the role of COX-1 and COX-2 elaborated prostaglandins in the recovery of intestinal barrier function by evaluating the effects of selective COX-1 and COX-2 inhibitors on mucosal recovery and eicosanoid production. Methods: Porcine ileal mucosa subjected to 45 minutes of ischaemia was mounted in Ussing chambers, and transepithelial electrical resistance was used as an indicator of mucosal recovery. Prostaglandins E, and E-2 (PGE) and 6-keto-PGF(1alpha) (the stable metabolite of prostaglandin I-2 (PGI(2))) were measured using ELISA. Thromboxane B-2 (TXB2, the stable metabolite of TXA(2)) Was measured as a likely . indicator of COX-1 activity. Results: Ischaemic injured tissues recovered to control levels of resistance within three hours whereas tissues treated with indomethacin (5 x 10(-6) M) failed to fully recover, associated with inhibition of eicosanoid production. Injured tissues treated with the selective COX-1 inhibitor SC-560 (5 x 10(-6) M) or the COX-2 inhibitor NS-398 (5 x 10(-6) M) recovered to control levels of resistance within three hours, associated with significant elevations of PGE and 6-keto-PGF(1alpha) compared with untreated tissues. However, SC-560 significantly inhibited TXB2 production whereas NS-398 had no effect on this eicosanoid, indicating differential actions of these inhibitors related to their COX selectivity. Conclusions: The results suggest that recovery of resistance is triggered by PGE and PGI(2), which may be elaborated by either COX-1 or COX-2.