Protective effect of DS-4574, a peptidoleukotriene receptor antagonist, against endotoxin-induced intestinal injury in rats.
We evaluated the protective effect of DS-4574 (6-(2-cyclohexylethyl)-[1,3,4]thiadiazolo[3,2-a]-1,2,3- triazolo[4,5-d]pyrimidin-9(3H)-one), a peptidoleukotriene receptor antagonist, against intestinal mucosal injury evoked by endotoxin in rats by exploring changes in hematocrit and plasma leakage along with morphological features. Treatment with Escherichia coli endotoxin (5 mg/kg i.v.) alone elicited hemoconcentration, vasocongestion and a marked mucosal necrosis. DS-4574 (10-50 mg/kg) effectively prevented these changes on either oral or intraduodenal administration. These results demonstrate that peptidoleukotrienes may be key mediators in the intestinal injury induced by endotoxin in rats.
Tabuchi
Y
Y
Exploratory Research Laboratories III, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Furuhama
K
K
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004926:Escherichia coli; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006400:Hematocrit; D007410:Intestinal Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000473:pathology; D020024:Leukotriene Antagonists; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000494:pharmacology*
D004731:Endotoxins; D020024:Leukotriene Antagonists; D008070:Lipopolysaccharides; D011743:Pyrimidines; D014230:Triazoles; C076052:DS 4574; C044101:endotoxin, Escherichia coli