Prevention of esophageal strictures in a caustic burn model using halofuginone, an inhibitor of collagen type I synthesis

Dan Arbell, Raphael Udassin, Benjamin Z. Koplewitz, Meir Ohana, Olga Genina, Mark Pines, Arnon Nagler

Research output: Contribution to journalArticlepeer-review

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 α1(I) and transforming growth factor-β signaling pathway. We tried to assess whether HF would have an effect on the formation of strictures after inducing caustic esophageal. Materials and 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.

Original languageEnglish
Pages (from-to)1632-1635
Number of pages4
JournalLaryngoscope
Volume115
Issue number9
DOIs
StatePublished - Sep 2005
Externally publishedYes

Keywords

  • Caustic injury
  • Esophageal stricture
  • Halofuginone

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