Halofuginone, an inhibitor of collagen type I synthesis, prevents postoperative adhesion formation in the rat uterine horn model

OBJECTIVE: The objective of this study was to evaluate the effects of halof uginone-a specific inhibitor of collagen type 1 synthesis-in preventing ute rine horn adhesion formation in rats. STUDY DESIGN: Adhesions were induced by scraping the rat uterine horns unti l capillary bleeding occurred. Halofuginone was either injected intraperito neally or administered orally. The number and severity of the adhesions wer e scored. Collagen alpha 1(l) gene expression was evaluated by in situ hybr idization; total collagen was estimated by sirius red staining. Collagen sy nthesis in response to halofuginone was evaluated in cells cultured from th e adhesions. RESULTS: Regardless of the administration procedure, halofuginone reduced s ignificantly the number and severity of the adhesions in a dose-dependent m anner. Halofuginone prevented the increase in collagen alpha 1(I) gene expr ession observed in the rats that underwent this procedure, thus affecting o nly the newly synthesized collagen but not the resident collagen. In cells derived from rat uterine horn adhesions, halofuginone induced dose-dependen t inhibition of collagen synthesis. CONCLUSIONS: Upregulation of collagen synthesis appears to play a critical role in the pathophysiologic mechanism of adhesion formation. Halofuginone could be used as an important means of understanding the role of collagen i n adhesion formation and might become a novel and promising antifibrotic ag ent for preventing adhesion formation after pelvic surgery.