Anti-inflammatory effects of U74389F in a rat model of intestinal ischemia/reperfusion injury.
OBJECTIVE
To investigate the role of eicosanoid generation and neutrophilic infiltration in the protective effects of U74389F against ischemia/reperfusion injury in the small intestines of rats.


METHODS
Prospective, randomized, controlled study.


METHODS
University research laboratory.


METHODS
Adult, male Sprague-Dawley rats weighing between 200 and 300 g.


METHODS
Groups (5-8) of rats treated with U74389F or vehicle were subjected to a sham operation and 30 mins of ischemia by occlusion of the superior mesenteric artery or 30 mins of ischemia followed by 60 or 120 mins of reperfusion. U74389F (2.5 mg/kg i.v.) or vehicle (citrate buffer) were slowly injected 2 mins before ischemia.


RESULTS
Ischemia significantly (p < .05) increased mucosal injury (0 [normal] to 5) in both U74389F and untreated rats. In contrast, U74389F significantly (p < .05) attenuated the severity of injury after reperfusion. In vehicle-treated rats, ischemia/reperfusion significantly reduced villus height in both U74389F and untreated groups. However, the surface epithelial layer was intact in the U74389F but not in the vehicle-treated group. In addition, compared with the vehicle-treated group, U74389F significantly reduced neutrophil infiltration and prevented the increase in leukotriene B4 and prostaglandin E2 in response to ischemia and reperfusion.


CONCLUSIONS
This study demonstrates that the mechanism of U74389F against mesenteric ischemia/reperfusion includes a delay and reduction of neutrophilic infiltrate, an inhibition of leukotriene B4 production, and a facilitation of mucosal restitution.
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D015232:Dinoprostone / Q000097:blood; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D015777:Eicosanoids / Q000096:biosynthesis / Q000276:immunology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000276:immunology; D007275:Injections, Intravenous; D007421:Intestine, Small / Q000098:blood supply*; D007975:Leukotriene B4 / Q000097:blood; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects / Q000276:immunology; D011281:Pregnatrienes / Q000627:therapeutic use*; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*