Background:

Setipafant is a platelet-activating factor (PAF) antagonist.

Animals are separated into six groups: U4, controls; S, sham operated animals undergoing laparotomy; I4 and I9, ligation of the mesenteric vessels in the last ileal loop; IT4 and IT9, same procedure together with treatment with Setipafant (50 mg/kg) orally before and after surgery and intraperitoneally during surgery. Animals are killed at day 4 in groups U4, S, I4 and IT4 and at day 9 in groups I9 and IT9, with histological studies and mediator measurements taken. Macroscopic and histological lesions of intestinal wall in groups I4, I9, IT4 and IT9 are similar to those of human neonatal necrotizing enterocolitis and do not vary according to the absence or the presence of Setipafant (BN 50727) treatment. Peritoneal bands are significantly reduced in treated groups IT4 and IT9 as compared with untreated ones I4 and I9. Mucosal PAF levels in the terminal ileum are higher in group I4 than in groups U4 or I9. In the upper loop, mucosal PAF levels are comparable in all groups. An increase in stool PAF levels is observed only in group I9, whereas values comparable to those observed in controls are detected in other groups[1]. Pretreatment of the animals with one or other of the structurally unrelated PAF receptor antagonists, BN 52021 (10 mg/kg, i.p.) or BN 50727 (1 mg/kg, i.p.) significantly reduces Dexamethasone-induced gastric damage. In these animals neither petechiae nor erosions are observed[2].

[1]. de Boissieu D, et al. Effect of BN 50727 on pathological findings and tissue platelet activating factor levels during ileal ischemia in newborn piglets. J Pediatr Surg. 1996 Dec;31(12):1675-9. [2]. Filep JG, et al. Dexamethasone-induced gastric mucosal damage in the rat: possible role of platelet-activating factor. Br J Pharmacol. 1992 Apr;105(4):912-8.