title: Antiadhesive and anti-inflammatory effects of pirfenidone in postoperative intra-abdominal adhesion in an experimental rat model.
abstract: BACKGROUND
  Pirfenidone (PF) is a potent antifibrotic and anti-inflammatory agent. We investigated the protective effect of PF against postoperative intra-abdominal adhesions.
  
  
  METHODS
  Thirty male Sprague-Dawley rats were divided into three groups (n = 10 in each group). In group 1 (control), adhesion induction was performed by cecal abrasion, and no treatment was administered. In group 2 (vehicle), for 2 wk after adhesion induction, 0.4%-carboxymethylcellulose was administered by gavage. In group 3 (PF treatment), for 2 wk after adhesion induction, 500-mg/kg/d PF was administered by gavage. On the 15th postoperative day, the animals were killed, and cecal and peritoneal tissues were excised. The adhesions were graded macroscopically. The protein concentrations and mRNA expression levels of the following genes were measured in the tissues: matrix metallopeptidase-9 (MMP-9); tissue inhibitor of metalloproteinase-1 (TIMP-1); tumor necrosis factor-alpha (TNF-α); and transforming growth factor-beta 1 (TGF-β1). The tissue samples were also evaluated histopathologically.
  
  
  RESULTS
  Macroscopic and histopathologic evaluation showed that PF-reduced adhesion and inflammation (P < 0.001, P = 0.004, respectively). Pretreatment with PF-reduced TIMP-1, TNF-α, and TGF-β1 protein concentrations (P < 0.001, P < 0.001, and P < 0.001, respectively) and mRNA expression levels (P = 0.030, P = 0.005, and P = 0.016, respectively) and increased MMP-9 protein concentrations (P < 0.001) and mRNA expression (P = 0.021).
  
  
  CONCLUSIONS
  The findings of this study suggest that PF can be used as a protective agent to prevent the development of peritoneal adhesions and inflammation during the postoperative period.
authors.affiliation: Department of General Surgery, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey. Electronic address: zulfubayhan@gmail.com.
authors.forename: Zulfu
authors.initials: Z
authors.lastname: Bayhan
authors.affiliation: Department of General Surgery, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey.
authors.forename: Sezgin
authors.initials: S
authors.lastname: Zeren
authors.affiliation: Department of Medical Biochemistry, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey.
authors.forename: Fatma Emel
authors.initials: FE
authors.lastname: Kocak
authors.affiliation: Department of Pathology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey.
authors.forename: Cengiz
authors.initials: C
authors.lastname: Kocak
authors.affiliation: Department of Physiology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey.
authors.forename: Raziye
authors.initials: R
authors.lastname: Akcılar
authors.affiliation: Department of General Surgery, Faculty of Medicine, Abant Izzet Baysal University, Bolu, Turkey.
authors.forename: Ertugrul
authors.initials: E
authors.lastname: Kargı
authors.affiliation: Department of General Surgery, Derince Education and Research Hospital, Kocaeli, Turkey.
authors.forename: Cagrı
authors.initials: C
authors.lastname: Tiryaki
authors.affiliation: Department of General Surgery, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey.
authors.forename: Faik
authors.initials: F
authors.lastname: Yaylak
authors.affiliation: Department of Experimental Animal Research Center, Faculty of Medicine, University of Dumlupinar, Kütahya, Turkey.
authors.forename: Aydın
authors.initials: A
authors.lastname: Akcılar
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology; D011183:Postoperative Complications / Q000517:prevention & control*; D011728:Pyridones / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D000267:Tissue Adhesions / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011728:Pyridones; C576839:TIMP1 protein, rat; C508962:Tgfb1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C093844:pirfenidone; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: Focal adhesions; Matrix metalloproteinase inhibitors; Matrix metalloproteinases; Peritoneal fibrosis; Pirfenidone; Postoperative complications