Effects of teduglutide on histological parameters of intestinal anastomotic healing

Abstract

Intestinal anastomotic failure continues to be one of the most relevant surgical incidents. Teduglutide is an enterotrophic long-acting equivalent of glucagon-like peptide-2 (GLP-2) recommended for the treatment of adult patients with short bowel syndrome. This study evaluates the effects of short-term teduglutide administration on histological parameters of intestinal anastomotic healing in an animal model. Wistar rats (n = 31) were submitted to ileal resection and standard anastomosis, with or without postoperative teduglutide ministration, and sacrificed at the third or seventh day with tissue and blood sampling. Intestinal anastomotic healing was assessed with the modified Houdart–Hutschenreiter classification after hematoxylin and eosin staining. Collagen content and distribution were evaluated with the Gordon and Sweet technique; neoangiogenesis and epithelial proliferation indexes with anti-CD31 and anti-Ki67 immunostaining, respectively. GLP-2 plasma levels were determined by quantitative enzyme immunoassay. Teduglutide administration was associated with higher levels of reepithelialization (P = 0.022) and a higher neoangiogenesis index (neovessel density = 16.0 ± 10.8/mm2 vs. 5.3 ± 3.4/mm2; P = 0.0001) at the seventh postoperative day. Lower expression of type I collagen (P = 0.015) and higher content of type III collagen (P = 0.007) in the submucosa were also documented at the seventh day in teduglutide-treated animals. Drug administration was not associated with statistically significant differences of GLP-2 plasma levels. These findings indicate a positive impact of teduglutide on the reepithelialization and neoangiogenesis events of the proliferative phase of intestinal anastomotic repair. Additional studies are necessary to clarify its effects on the fibrogenesis process.