title: Pirfenidone prevents rat esophageal stricture formation.
abstract: BACKGROUND
  Accidental ingestion of caustic substances induces esophageal injuries and stenosis formation. The main aim for acute phase treatment is to prevent esophageal stenosis. Pirfenidone (PFD) is a pyridone with antifibrotic and anti-inflammatory effects. Esophagus stenosis takes place after a strong inflammation process where proinflammatory and profibrogenic cytokines play an important role. The present study investigates the efficacy of PFD on the prevention of stricture development after esophageal caustic injuries in a rat model.
  
  
  METHODS
  Caustic esophageal burn was produced by application of 32% of NaOH to the distal esophagus of healthy rats. PFD in the form of 8% gel was administered at a dose of 200 mg/kg/d. Animals were divided in three experimental groups as follows: healthy rats, animals injured with NaOH without PFD treatment, and rats injured with NaOH and treated with PFD. Efficacy of the treatment was assessed by measuring image esophagoscopy and esophagography with contrast barium at the 21st d. Histology staining with Sirius-red was performed to evaluate collagen deposition and stenosis area. Gene expression of transforming growth factor β1, collagen-1, plasminogen activator inhibitor-1, connective tissue growth factor, and matrix metalloproteinase 2 were measured by quantitative reverse transcription polymerase chain reaction.
  
  
  RESULTS
  There was significant difference in means of stenosis by esophagoscopy and esophagogram. Collagen deposition in the damaged area increased significantly when rats were burned with NaOH, and decreased notably in PFD treated group. Profibrogenic key molecules transforming growth factor β1, collagen 1, plasminogen activator inhibitor-1 and connective tissue growth factor expression were significantly lower respect to control group without PFD treatment where matrix metalloproteinase 2 expression was no different in all groups.
  
  
  CONCLUSIONS
  This study suggests that PFD reduces stenosis on caustic esophageal burn by decreasing profibrogenic genes expression and ameliorates fibrosis significantly in the chronic phase.
authors.affiliation: Department of Pediatric Surgery, OPD Hospital Civil de Guadalajara FAA, Guadalajara, Jalisco, México.
authors.forename: J
authors.initials: J
authors.lastname: Orozco-Perez
authors.affiliation: Department of Pediatric Surgery, OPD Hospital Civil de Guadalajara FAA, Guadalajara, Jalisco, México.
authors.forename: O
authors.initials: O
authors.lastname: Aguirre-Jauregui
authors.affiliation: Department of Molecular Biology and Genomics, Institute for Molecular Biology and Gene Therapy, University of Guadalajara, Guadalajara, México.
authors.forename: A M
authors.initials: AM
authors.lastname: Salazar-Montes
authors.affiliation: Department of Molecular Biology and Genomics, Institute for Molecular Biology and Gene Therapy, University of Guadalajara, Guadalajara, México.
authors.forename: A A
authors.initials: AA
authors.lastname: Sobrevilla-Navarro
authors.affiliation: Department of Molecular Biology and Genomics, Institute for Molecular Biology and Gene Therapy, University of Guadalajara, Guadalajara, México.
authors.forename: M S
authors.initials: MS
authors.lastname: Lucano-Landeros
authors.affiliation: Department of Molecular Biology and Genomics, Institute for Molecular Biology and Gene Therapy, University of Guadalajara, Guadalajara, México; Research Department, INNOVARE, Guadalajara, Jalisco, México. Electronic address: armdbo@gmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Armendáriz-Borunda
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004940:Esophageal Stenosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004941:Esophagitis / Q000139:chemically induced / Q000188:drug therapy; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011728:Pyridones / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar; D012972:Sodium Hydroxide; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C526316:CCN2 protein, rat; D017395:Plasminogen Activator Inhibitor 1; D011728:Pyridones; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D012972:Sodium Hydroxide; C093844:pirfenidone
keywords: Caustic esophageal stenosis; Fibrogenic esophageal stenosis; Pirfenidone; RT-PCR; Sirius-red stain