PROTECTIVE EFFECT OF DS-4574, A PEPTIDOLEUKOTRIENE RECEPTOR ANTAGONIST, AGAINST ENDOTOXIN-INDUCED INTESTINAL INJURY IN RATS

We evaluated the protective effect of DS-4574 [3,2-a]-1,2,3-triazolo[4 ,5-d]pyrimidin-9(3H)-one), a peptidoleukotriene receptor antagonist, a gainst intestinal mucosal injury evoked by endotoxin in rats by explor ing changes in hematocrit and plasma leakage along with morphological features. Treatment with Escherichia coli endotoxin (5 mg/kg i.v.) alo ne elicited hemoconcentration, vasocongestion and a marked mucosal nec rosis. DS-4574 (10-50 mg/kg) effectively prevented these changes on ei ther oral or intraduodenal administration. These results demonstrate t hat peptidoleukotrienes may be key mediators in the intestinal injury induced by endotoxin in rats.