Nintedanib, a multitarget tyrosine kinase inhibitor, suppresses postoperative peritoneal adhesion formation in a rat model

Background: Nintedanib is an antifibrotic agent approved by the United States Food and Drug Administration for the treatment of lung fibrosis. This study aimed to evaluate the efficacy of nintedanib for the prevention of postoperative peritoneal adhesion formation in a rat model. Methods: Eighteen female Sprague-Dawley rats underwent peritoneal ischemic button creation to induce peritoneal adhesion formation and were randomly allocated to receive 1 mL saline, 50 mg/kg nintedanib, or 100 mg/kg nintedanib by gavage once daily for 7 days. Peritoneal adhesion evaluation and histological and immunochemical examinations were performed on postoperative day 7. Twelve additional Sprague-Dawley rats underwent ileal resection and anastomosis and were randomized to receive saline or 100 mg/kg nintedanib by gavage once daily for 7 days. Anastomotic bursting pressure was assessed on postoperative day 7. Results: All rats survived until death 7 days after surgery without complications. Peritoneal adhesion incidence, quality, and tenacity were lower in both nintedanib groups than in the saline group (P < .01), but no differences were found between the 2 nintedanib groups (P > .05). Histological and immunochemical results demonstrated less inflammation, fibrosis, collagen, and cell proliferation and fewer myofibroblasts in the ischemic buttons treated with 50 mg/kg or 100 mg/kg nintedanib than in those treated with saline (P < .01), but no difference was found between the 2 nintedanib groups (P > .05). Anastomotic bursting pressures were not significantly different between the saline and nintedanib groups (P > .05). Conclusion: Nintedanib is effective for the prevention of postoperative peritoneal adhesion formation in a rat model. (c) 2021 Elsevier Inc. All rights reserved.