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Prevention of Esophageal Strictures in a Caustic Burn Model Using Halofuginone, an Inhibitor of Collagen Type I Synthesis
Author(s) -
Arbell Dan,
Udassin Raphael,
Koplewitz Benjamin Z.,
Ohana Meir,
Genina Olga,
Pines Mark,
Nagler Ar
Publication year - 2005
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1097/01.mlg.0000176551.09051.f2
Subject(s) - esophageal stricture , esophagus , medicine , fibrosis , gastroenterology , esophageal disease , caustic (mathematics) , chemical burn , surgery , physics , mathematical physics
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.