The effect of halofuginone, a specific inhibitor of collagen type 1 synthesis, in the prevention of esophageal strictures related to caustic injury

Am J Surg. 2004 Feb;187(2):257-60. doi: 10.1016/j.amjsurg.2003.11.008.

Abstract

Background: To assess the effects of halofuginone, a specific inhibitor of synthesis of collagen type 1, which is the major constituent of fibrosis, on esophageal stricture formation due to caustic ingestion.

Methods: Sixty rats were divided into four equal groups: control group; sham laparotomy group; caustic injury without treatment group; caustic injury with halofuginone treatment group. Caustic injuries were done by 50% sodium hydroxide. Halofuginone was administered by the first postoperative day. All animals were sacrificed on day 21; and the results were evaluated by hydroxyproline levels, stenosis index, lumen diameter, histopathological evaluation, wall thickness, and animal weights.

Results: Mortality differences were significant comparing group 3 with group 1 and 2 (P = 0.006) and group 4 (P = 0.03). According to hydroxyproline levels, the differences are significantly higher (P <0.001) comparing group 3 with group 1, 2, and 4. The P value was considered significant in all other parameters (P <0.001) for all the groups but group 1 versus group 2 (P >0.05).

Conclusions: Halofuginone, a specific inhibitor of collagen type 1 synthesis, significantly reduced esophageal stricture occurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Burns, Chemical / complications
  • Burns, Chemical / drug therapy*
  • Caustics
  • Collagen Type I / antagonists & inhibitors*
  • Esophageal Stenosis / etiology
  • Esophageal Stenosis / prevention & control*
  • Esophagus / drug effects*
  • Esophagus / pathology
  • Fibrosis
  • Injections, Intraperitoneal
  • Male
  • Models, Animal
  • Piperidines
  • Protein Synthesis Inhibitors / administration & dosage
  • Protein Synthesis Inhibitors / pharmacology*
  • Quinazolines / administration & dosage
  • Quinazolines / pharmacology*
  • Quinazolinones
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Hydroxide

Substances

  • Caustics
  • Collagen Type I
  • Piperidines
  • Protein Synthesis Inhibitors
  • Quinazolines
  • Quinazolinones
  • Sodium Hydroxide
  • halofuginone