Setipafant

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].