Abstract

Objectives: Intra-abdominal adhesions are the most frequently occurring postoperative complication following abdominopelvic surgery. Peritoneal adhesion formation can lead to infertility, chronic pelvic pain, and intestinal obstruction. Several studies have shown the potential role of metformin in reducing inflammation. Here, we explored the therapeutic potency of Metformin against postsurgical adhesion band formation.

Methods: We adopted Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines for the experimental protocol. Peritoneal adhesions were examined macroscopically .Metformin (100 mg/kg) was administered intraperitoneally in male albino Wistar rats. After 9 days, macroscopic evidence and score of fibrotic bands based on scaling methods were performed and evaluated by the Nair and Leach scoring system. Moreover, the anti-inflammatory and antifibrosis effects were investigated by using hematoxylin and eosin, Masson's trichrome staining, the enzyme-linked immunosorbent assay (ELISA), and reverse transcription polymerase chain reaction (RT-PCR).

Results: Metformin inhibited the stabilization of adhesion bands and appeared to elicit antiinflammatory responses by attenuating submucosal edema, suppressing proinflammatory cytokines, decreasing proinflammatory cell infiltration, and inhibiting oxidative stress at the site of peritoneal surgery. We also showed that metformin prevents fibrotic adhesion band formation by reducing excessive collagen deposition and suppression of profibrotic gene expression at the peritoneum adhesion tissues via modulation of Col 1A1/A3.

Conclusion: These results supported the potential application of metformin in preventing postsurgical adhesion band formation by inhibiting key pathologic responses of inflammation and fibrosis in patients post-surgery.

Keywords: Intra-abdominal adhesion, inflammatory response, metformin, transforming growth factor beta, fibrosis, RT-PCR.