title: Effect of Pirfenidone on Vascular Proliferation, Inflammation and Fibrosis in an Abdominal Adhesion Rat Model.
abstract: OBJECTIVE
  To study the efficacy of pirfenidone for prevention of postoperative adhesion formation in an adhesion rat model.
  
  
  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.
  
  
  CONCLUSIONS
  Pirfenidone is an effective agent on the prevention of postoperative vascular proliferation, inflammation and fibrosis in scarred tissue particularly with intraperitoneal administration.
authors.affiliation: a Department of Obstetrics and Gynecology , Celal Bayar University School of Medicine , Manisa , Turkey.
authors.forename: Pinar Solmaz
authors.initials: PS
authors.lastname: Hasdemir
authors.affiliation: b Department of Histology and Embryology , Celal Bayar University School of Medicine , Manisa , Turkey.
authors.forename: Mahmud
authors.initials: M
authors.lastname: Ozkut
authors.affiliation: a Department of Obstetrics and Gynecology , Celal Bayar University School of Medicine , Manisa , Turkey.
authors.forename: Tevfik
authors.initials: T
authors.lastname: Guvenal
authors.affiliation: b Department of Histology and Embryology , Celal Bayar University School of Medicine , Manisa , Turkey.
authors.forename: Melis Aylin
authors.initials: MA
authors.lastname: Uner
authors.affiliation: a Department of Obstetrics and Gynecology , Celal Bayar University School of Medicine , Manisa , Turkey.
authors.forename: Esat
authors.initials: E
authors.lastname: Calik
authors.affiliation: a Department of Obstetrics and Gynecology , Celal Bayar University School of Medicine , Manisa , Turkey.
authors.forename: Semra Oruc
authors.initials: SO
authors.lastname: Koltan
authors.affiliation: a Department of Obstetrics and Gynecology , Celal Bayar University School of Medicine , Manisa , Turkey.
authors.forename: Faik Mumtaz
authors.initials: FM
authors.lastname: Koyuncu
authors.affiliation: b Department of Histology and Embryology , Celal Bayar University School of Medicine , Manisa , Turkey.
authors.forename: Kemal
authors.initials: K
authors.lastname: Ozbilgin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D020381:Interleukin-17 / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010537:Peritoneum / Q000473:pathology; D011183:Postoperative Complications / Q000517:prevention & control*; D011728:Pyridones / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D000267:Tissue Adhesions / Q000378:metabolism / Q000517:prevention & control*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016896:Treatment Outcome; D014599:Uterus / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C515934:Il17a protein, rat; D020381:Interleukin-17; D011728:Pyridones; D016212:Transforming Growth Factor beta; C093844:pirfenidone
keywords: Adhesion; fibrosis; interleukin-17; pirfenidone; rat; transforming growth factor-β