Impact of pirfenidone administration routes on colon anastomosis and healing in rats

Abstract

Introduction: Anastomotic strictures are a prevalent complication in colorectal surgery. This study aimed to investigate the antifibrotic effects of pirfenidone on colorectal anastomotic stenosis, abdominal wall wound healing, and adhesion formation in a rat model by comparing various routes of administration (intraperitoneal, oral, and rectal). Methods: Forty female Wistar Albino rats were randomly allocated to four groups: control, intraperitoneal pirfenidone administration (IAP), oral pirfenidone administration, and rectal pirfenidone administration. Colonic anastomosis was performed followed by pirfenidone administration for 14 d. This study evaluated burst pressure, histopathological parameters, immunohistochemical analyses, and molecular analyses of transforming growth factor-β, vascular endothelial growth factor-A, and fibroblast growth factor-2 expression. Results: Burst pressure increased significantly across all treatment groups, with IAP and rectal pirfenidone administration demonstrating a three-fold increase compared with the control. Histopathological analysis revealed enhanced inflammatory cell infiltration, fibroblastic activity, collagen deposition, and neoangiogenesis in the treatment groups. Transforming growth factor-βexpression increased in all treatment groups, whereas vascular endothelial growth factor-A and fibroblast growth factor-2 expressions decreased. Intra-abdominal adhesions decreased across all treatment groups, with IAP exhibiting the most substantial reduction. Anastomosis width increased in all treatment groups, with oral pirfenidone administration demonstrating the widest anastomosis. Conclusions: Pirfenidone exhibited a significant antifibrotic effect by preventing colorectal anastomotic stenosis, reducing intra-abdominal adhesions, and promoting optimal wound healing. Oral administration resulted in the widest anastomotic lumen, suggesting its potential as the preferred route for clinical applications. Further research is necessary to elucidate the long-term impact of pirfenidone on anastomotic healing and optimize its therapeutic potential