Recovery of ischaemic injured porcine ileum: evidence for a contributory role of COX-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.


OBJECTIVE
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 E1 and E2 (PGE) and 6-keto-PGF1alpha (the stable metabolite of prostaglandin I2 (PGI2)) were measured using ELISA. Thromboxane B2 (TXB2, the stable metabolite of TXA2) 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 (5x10(-6) M) failed to fully recover, associated with inhibition of eicosanoid production. Injured tissues treated with the selective COX-1 inhibitor SC-560 (5x10(-6) M) or the COX-2 inhibitor NS-398 (5x10(-6) M) recovered to control levels of resistance within three hours, associated with significant elevations of PGE and 6-keto-PGF1alpha 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 PGI2, which may be elaborated by either COX-1 or COX-2.
Blikslager
A T
AT
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA. Anthony_Blikslager@ncsu.edu
Zimmel
D N
DN
Young
K M
KM
Campbell
N B
NB
Little
D
D
Argenzio
R A
RA
D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015194:Diffusion Chambers, Culture; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000096:biosynthesis; D005260:Female; D007082:Ileum / Q000098:blood supply* / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D007511:Ischemia / Q000201:enzymology* / Q000473:pathology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology; D010539:Permeability; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D013552:Swine
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D007527:Isoenzymes; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin