title: Prevention of esophageal strictures in a caustic burn model using halofuginone, an inhibitor of collagen type I synthesis.
abstract: OBJECTIVE
  Esophageal strictures caused by caustic injury continue to be a plaguing problem. Halofuginone (HF) has been proven to inhibit the formation of fibrosis in various animal models and human diseases. Its mechanism appears to be through the suppression of the production of collagen alpha1(I) and transforming growth factor-beta signaling pathway. We tried to assess whether HF would have an effect on the formation of strictures after inducing caustic esophageal.
  
  
  METHODS
  Esophageal injury was caused by injecting 25% NaOH to an isolated esophageal segment. Study group rats were treated with HF orally for 3 consecutive days before the injury and afterward. Control group rats received regular chow. The results were evaluated by upper gastrointestinal series (UGI) and through pathologic studies.
  
  
  RESULTS
  HF treatment resulted in marked improvement in the esophageal strictures. The UGI series showed esophageal patency of 73% (45%-100%) in the treated animals (n = 7) as compared with almost no patency, 11% (5-16%), in the controls (n = 4) (P = .018). The histologic examination showed significantly less stricture and scarring in the treated group. Whereas the ratio between the esophageal wall thickness to mucosal thickness was 2.34 +/- 0.23 in the study group, the control group had a ratio of 9.56 +/- 0.69 (P = .0044). Finally, whereas 86% of the study group survived, all the rats in the control group died by day 20.
  
  
  CONCLUSIONS
  HF modulated the wound healing reaction caused by caustic injury of the esophagus in a rat model, resulting in increased esophageal patency, reduction in esophageal wall thickness, and increased survival.
authors.affiliation: Department of Pediatric Surgery, Hadassah University Hospital, Kyriat Hadassah, PO Box 12000, 91120 Jerusalem, Israel. arbell@hadassah.org.il
authors.forename: Dan
authors.initials: D
authors.lastname: Arbell
authors.forename: Raphael
authors.initials: R
authors.lastname: Udassin
authors.forename: Benjamin Z
authors.initials: BZ
authors.lastname: Koplewitz
authors.forename: Meir
authors.initials: M
authors.lastname: Ohana
authors.forename: Olga
authors.initials: O
authors.lastname: Genina
authors.forename: Mark
authors.initials: M
authors.lastname: Pines
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000818:Animals; D002057:Burns, Chemical / Q000150:complications*; D002424:Caustics / Q000009:adverse effects*; D024042:Collagen Type I / Q000096:biosynthesis*; D004940:Esophageal Stenosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D066298:In Vitro Techniques; D010880:Piperidines; D011500:Protein Synthesis Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D052999:Quinazolinones; D011859:Radiography; D051381:Rats; D012972:Sodium Hydroxide / Q000009:adverse effects; D016212:Transforming Growth Factor beta / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D002424:Caustics; D024042:Collagen Type I; D010880:Piperidines; D011500:Protein Synthesis Inhibitors; D011799:Quinazolines; D052999:Quinazolinones; D016212:Transforming Growth Factor beta; D012972:Sodium Hydroxide; C010176:halofuginone