Protective effect of a novel antioxidant non-steroidal anti-inflammatory agent (compound IA) on intestinal viability after acute mesenteric ischemia and reperfusion.
Reactive oxygen species play an important role in the basic pathophysiology of ischemia-reperfusion injury. We investigated whether the administration of a novel non-steroidal anti-inflammatory compound with antioxidant properties, the compound [5-(2-amino-ethylamino)-1-phenyl-2-pentanone] (compound IA), has a beneficial effect on the repair process of the intestinal mucosa after transient mesenteric ischemia in a randomized blind trial. Six groups of rats were subjected to a model of 60 min of intestinal ischemia that was produced by occluding the superior mesenteric artery. At the end of ischemia, compound IA was administered intravenously and the clamp was removed allowing reperfusion. At 60 min after reperfusion, animals were sacrificed and a 10 cm section of terminal ileum was resected. The outcome was evaluated by histopathologic assessment, measurement of polymorphonuclear leukocytes and the extent of lipid peroxidation measuring the small intestine tissue malondialdehyde. After 1 h of reperfusion, the mucosal damage was less in IA-treated rats compared with the control group. Moreover, the number of polymorphonuclear leukocytes in intestinal mucosa was significantly lower in IA group. Compound IA resulted in a statistically significant reduction of the concentration of small intestine tissue malondialdehyde, compared to those of controls. Administration of compound IA decreased the mucosal damage in rats that were subjected to 60 min of ischemia followed by 60 min of reperfusion. The mechanism of compound IA action is considered to be mediated via its potent antioxidant, free radical scavenging activities and inhibition of polymorphonuclear leukocytes infiltration.
Poussios
Dimitrios
D
3rd Department of Surgery, "Sotiria" Hospital, University of Athens School of Medicine, Athens, Greece.
Andreadou
Ioanna
I
Papalois
Apostolos
A
Rekka
Eleni
E
Gavalakis
Nikolaos
N
Aroni
Kyriaki
K
Kourounakis
Panos N
PN
Fotiadis
Constantinos
C
Sechas
Michael N
MN
D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D005021:Ethylamines / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects*; D007421:Intestine, Small / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D007511:Ischemia / Q000150:complications / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D017538:Mesenteric Artery, Superior / Q000473:pathology; D008641:Mesenteric Vascular Occlusion / Q000150:complications; D020556:Neutrophil Infiltration / Q000187:drug effects; D010420:Pentanes / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*
C481250:5-(2-amino-ethylamino)-1-phenyl-2-pentanone; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D005021:Ethylamines; D016166:Free Radical Scavengers; D010420:Pentanes; D008315:Malondialdehyde