The beneficial effect of a new anti-inflammatory compound with antioxidant properties (IA) and of U-74389G (21-Lazaroid) on intestinal recovery after acute mesenteric ischemia and reperfusion in rats

We investigated whether the administration of a novel antiinflammatory compound with antioxidant properties (IA) and of the aminolazaroid U-74389G has a beneficial effect on the repair process of the intestinal mucosa after transient mesenteric ischemia. The administration took place in a clinical setting (i.e. after the onset of ischemia). Randomized, blinded trial in animal laboratory was performed. 54 male Wistar rats were studied in nine intervention groups. The rats weighing 300-350gr, were housed in plastic cages under standardized conditions (23°C, 60% relative humidity, 12hr light and 12hr dark cycles). Groups 1, 4 and 7 were the groups of sham-operated animals. Groups 2, 5 and 8 were the groups of ischemia. Finally, groups 3, 6 and 9 were the groups where the ischemia/reperfusion protocol was applied. Intestinal ischemia was produced in anesthetized rats by occluding the superior mesenteric artery (SMA) for 60 mins with a microvascular clamp. At the end of ischemia, normal saline, IA or U-74389G was administered intravenously and the clamp was removed allowing reperfusion (groups 3, 6 and 9 respectively). At 60 mins after reperfusion animals were sacrificed and a 10 cm section of terminal ileum was resected. Intestinal mucosa morphology and presence of polymorphonuclear leucocytes (PMN’s) were determined by two blinded observers. All groups had intestinal mucosal injury following ischemia, but after 1 hour of reperfusion the mucosal damage was less in IA-treated rats compared with the control and U74389G rats, which was statistically significant. Moreover, the number of PMN’s in intestinal mucosa was significantly lower in IA group. IA and U-74389G did not prevent ischemic damage of the mucosa. However, they did accelerate the repair of the mucosa after reperfusion. IA acted at a statistically significant level while U-74389G did not. The mechanism of IA action must be through its potent antioxidant, free radical scavenging activity and PMN infiltration. The increased number of mucosa cells in mitosis and their role in mucosal repair should be studied further.