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

Abstract

The objective of this study was to evaluate the effects of halofuginone-a specific inhibitor of collagen type I synthesis-in preventing uterine horn adhesion formation in rats. Adhesions were induced by scraping the rat uterine horns until capillary bleeding occurred. Halofuginone was either injected intraperitoneally or administered orally. The number and severity of the adhesions were scored. Collagen alpha1(I) gene expression was evaluated by in situ hybridization; total collagen was estimated by sirius red staining. Collagen synthesis in response to halofuginone was evaluated in cells cultured from the adhesions. Regardless of the administration procedure, halofuginone reduced significantly the number and severity of the adhesions in a dose-dependent manner. Halofuginone prevented the increase in collagen alpha1(I) gene expression observed in the rats that underwent this procedure, thus affecting only the newly synthesized collagen but not the resident collagen. In cells derived from rat uterine horn adhesions, halofuginone induced dose-dependent inhibition of collagen synthesis. 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 in adhesion formation and might become a novel and promising antifibrotic agent for preventing adhesion formation after pelvic surgery.