Trefoil factor family peptide 3 prevents the development and promotes healing of ischemia-reperfusion injury in weanling rats

Background/Purpose: Although the pathogenesis of necrotizing enterocolitis (NEC) is not completely defined, ischemia appears to be one of the most important causative factors. Trefoil factor family peptide 3 (TFF3) is a peptide normally expressed in the small bowel and colon and is involved in the maintenance and repair of mucosal integrity. The authors hypothesized that monomeric (TFF3 Ser(57)) and dimeric (TFF3 Cys(57)) recombinant TFF3 may prevent the development and accelerate healing of intestinal ischemia-reperfusion injury in weanling rats. Methods: Intestinal injury was induced in 18-day-old rats by occlusion of the superior mesenteric vessels for 60 minutes. To examine the protective effect, rats were given 3 mug/g of TFF3 Ser(57) or TFF3 Cys(57) by subcutaneous or enteral administration 30 minutes before the vascular occlusion. To examine the healing effect, rats were given 3 mug/g of TFF3 Ser(57) or TFF3 Cys(57) by subcutaneous or enteral administration 60 minutes after the beginning of reperfusion. Samples from small bowel and colon were collected for morphometric analysis after 3 hours of reperfusion. Mucosal damage was assessed by the Chiu score. Results: Both forms of TFF3 reduced the amount of damage when administered before the ischemia. Administration of TFF3 Ser(57) and TFF3 Cys(57) after the beginning of reperfusion significantly increased the villous height and decreased the Chiu score in the small intestine and colon. Conclusions: TFF3 Ser(57) monomer and TFF3 Cys(57) dimer prevent the development and promote healing of ischemia-reperfusion injury in weanling rats. There are no differences between the routes of administration of TFF3. (C) 2004 Elsevier Inc, All rights reserved.