THE EFFECTS OF SELECTIVE COX-2 INHIBITORS ON LOCAL AND REMOTE INTESTINAL ISCHEMIA/REPERFUSION INJURY IN RATS
László Szilvia Bianka
Gyógyszertudományok
Dr. Zelkó Romána
SE Farmakológiai és Farmakoterápiás Intézet Knoll József terem
2026-01-27 15:30:00
Experimentális és klinikai farmakológia
Dr. Szökő Éva
Dr. Zádori Zoltán
Dr. Müllner Katalin
Dr. Venglovecz Viktória
Dr. Zsembery Ákos
Dr. Tábi Tamás
Dr. Mike Árpád
Myocardial I/R can induce remote organ injury, including that of the small intestine, which may contribute to its overall morbidity and mortality. Therefore, we investigated whether cardiac I/R elicits early remote alterations in the intestinal tissue and whether prolonged administration of rofecoxib - a selective COX-2 inhibitor - can attenuate these effects. Notably, histopathological examination revealed mild mucosal inflammation in the small intestine as early as two hours following cardiac I/R, which was independent of cardiac I/R-induced altered mesenteric perfusion. The intestinal involvement and the protective effect of rofecoxib were correlated with elevated plasma activity of MMP-2 but not MMP-9. Rofecoxib appears to exert protective effects on remote intestinal tissues, potentially through cardioprotection via infarct size reduction. These findings suggest that plasma MMP-2 may serve as an early biomarker for cardiac I/R-induced intestinal injury.
As rofecoxib was shown to be protective in remote I/R-induced small intestinal injury in the previous model, it was chosen as a test compound in the study of mesenteric I/R, which still has a high mortality rate in clinical practice. We also applied celecoxib as a clinically used selective COX-2 inhibitor in the local intestinal I/R injury model.
Celecoxib was more effective compared to rofecoxib in alleviating I/R-induced small intestinal inflammation in rats. Celecoxib demonstrated anti-inflammatory effects only at higher doses, at which it lost its selectivity for COX-2. This suggests that COX-2 inhibition alone may not be sufficient to prevent I/R-induced intestinal damage, and that COX-1 may also play a role in the pathological process. However, neither celecoxib, even at high doses, nor rofecoxib was able to prevent the histological damage induced by mesenteric I/R. The pro-apoptotic properties of celecoxib may explain its lack of protective effect against tissue injury, despite its anti-inflammatory actions. Moreover, rofecoxib was found to reduce Akt phosphorylation during I/R, which may account for its limited anti-inflammatory efficacy.
