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

Abstract

SUMMARY
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
(PMNs) 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 U-
74389G rats, which was statistically significant. Moreover,
the number of PMNs 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.
Key words: Intestine, Ischemia, Oxidative stress, Experimental
colitis, Reperfusion, Aminolazaroid, U-74389G, Mucosal
damage, Neutrophils, Lipid peroxidation, Anti-inflammatory
agents