Prevention of esophageal strictures in a caustic burn model using halofuginone, an inhibitor of collagen type I synthesis.
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.
Arbell
Dan
D
Department of Pediatric Surgery, Hadassah University Hospital, Kyriat Hadassah, PO Box 12000, 91120 Jerusalem, Israel. arbell@hadassah.org.il
Udassin
Raphael
R
Koplewitz
Benjamin Z
BZ
Ohana
Meir
M
Genina
Olga
O
Pines
Mark
M
Nagler
Arnon
A
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
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