Effect of Pirfenidone on Vascular Proliferation, Inflammation and Fibrosis in an Abdominal Adhesion Rat Model
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2017
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Abstract
Aim: To study the efficacy of pirfenidone for prevention of postoperative adhesion formation in an adhesion rat model. Materials and Methods: Eighteen female Wistar rats were subjected to right-sided parietal peritoneum and right uterine horn adhesion model. Rats were randomized into three groups: group 1 (control) (closure of midline abdominal incision without any agent administration), group 2 (closure of incision after intraperitoneal administration of pirfenidone), and group 3 (closure of incision and only oral administration of pirfenidone for 14 days). Relaparotomy was performed 14 days after the first surgery. Effect of pirfenidone on adhesion formation was assessed on light microscopy by scoring vascular proliferation, inflammation, fibrosis, and collagen formation in the scarred tissue. Effect of pirfenidone on inflammation was assessed by measurement of transforming growth factor-β and interleukin-17 levels in scarred tissue. Results: The degree of vascular proliferation (1.32 ± 0.39 versus 2.34 ± 0.46, p < 0.001), inflammation (1.60 ± 0.70 versus 2.60 ± 0.52, p < 0.01), and fibrosis (1.50 ± 0.53 versus 2.40 ± 0.52, p < 0.01) were less prominent in group 2 compared to group 1, respectively. Only vascular proliferation was found to be less prominent in group 3 compared to group 1 (1.60 ± 0.42 versus 2.34 ± 0.46, p < 0.01). Intraperitoneal and oral administration of pirfenidone reduced tissue levels of inflammatory markers (TGF-β and IL-17) in parietal and visceral peritoneum compared to control group. Intraperitoneal administration of pirfenidone compared to oral administration was more effective in reducing tissue levels of inflammatory markers. Conclusion: Pirfenidone is an effective agent on the prevention of postoperative vascular proliferation, inflammation and fibrosis in scarred tissue particularly with intraperitoneal administration. Copyright © 2017 Taylor & Francis Group, LLC.
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Administration, Oral , Animals , Anti-Inflammatory Agents, Non-Steroidal , Disease Models, Animal , Female , Inflammation , Injections, Intraperitoneal , Interleukin-17 , Neovascularization, Pathologic , Peritoneum , Postoperative Complications , Pyridones , Rats , Rats, Wistar , Tissue Adhesions , Transforming Growth Factor beta , Treatment Outcome , Uterus , interleukin 17 , pirfenidone , transforming growth factor beta , IL17 protein, rat , interleukin 17 , nonsteroid antiinflammatory agent , pirfenidone , pyridone derivative , transforming growth factor beta , animal experiment , animal model , Article , collagen synthesis , controlled study , drug effect , drug efficacy , female , fibrosis , immunohistochemistry , inflammation , microscopy , nonhuman , peritoneum adhesion , peritoneum cell , physical disease by etiology and pathogenesis , priority journal , prophylaxis , uterus horn , vascular proliferation , Wistar rat , animal , disease model , inflammation , intraperitoneal drug administration , metabolism , neovascularization (pathology) , oral drug administration , pathology , peritoneum , postoperative complication , rat , tissue adhesion , treatment outcome , uterus