PhD Scientific Days 2021

PH_II_P: Pharmaceutical Sciences II. Posters

Chronic Administration of Selective COX-2 Inhibitors Ameliorates Mesenteric Ischemia/Reperfusion Injury

Text of the abstract

Introduction: Mesenteric ischemia is associated with high mortality. Furthermore, intestinal injury could be paradoxically aggravated by the restoration of blood flow, resulting in ischemia/reperfusion (I/R) injury. Upregulation of cyclooxygenase-2 (COX-2) is an early event during intestinal I/R, but it is still not clear, whether selective COX-2 inhibitors aggravate or ameliorate I/R injury. Aim: To evaluate the effect of chronic treatment with selective COX-2 inhibitors on intestinal I/R injury. Methods: Male Wistar rats (220-350 g) were treated with selective COX-2 inhibitors, celecoxib (10, 100 mg/kg) or rofecoxib (5, 50 mg/kg) intragastrically once daily for 7 days. Control animals were treated with vehicle. On the 8th day, rats underwent upper midline laparotomy and the superior mesenteric artery (SMA) was occluded for 30 minutes followed by 120 minutes of reperfusion. SMA was only manipulated in SHAM-operated animals. At the end of the protocol, animals were sacrificed and samples were taken from the distal jejunum for the determination of the tissue levels of different mediators. Results: Mesenteric IR induced significant elevation of mucosal myeloperoxidase (MPO), interleukin-1β (IL-1β) and IL-10. A 7-day treatment with celecoxib had no effect on the body weight or general condition of animals, but reduced the intestinal MPO protein level in a dose-dependent manner. In addition, celecoxib treatment, applied in both doses, significantly reduced IL-1β level, and tended to decrease IL-10. Rofecoxib in both applied doses decreased IL-1β mRNA in IR-subjected rats, but it failed to reduce the levels of MPO and IL-10. Conclusion: Celecoxib dose-dependently alleviated the IR-induced intestinal injury according to level of inflammatory mediators. Rofecoxib appears to be less effective in this model, but further experiments are needed to confirm it. Our study suggest that chronic treatment with COX-2 inhibitors may reduce the severity of intestinal I/R injury. Funding: The research was supported by the New National Excellence Program of the Ministry of Human Capacities (ÚNKP-20-3) and Semmelweis 250+ Excellence PhD grant (EFOP-3.6.3-VEKOP-16-00009).

University and Doctoral School

Semmelweis University, Doctoral School of Pharmaceutical Sciences