Halofuginone-an Inhibitor of Collagen Type I Synthesis-Prevents Postoperative Formation of Abdominal Adhesions

Abstract

ObjectiveTo evaluate the effects of halofuginone, a specific inhibitor of collagen type synthesis, on the postoperative formation of abdominal adhesions in rats. Summary Background Data ResultsThe adhesions formed between the intestinal walls were composed of collagen and were populated with cells expressing the collagen al (1) gene. Regardless of the administration procedure, halofuginone significantly reduced the number and severity of the adhesions. Halofuginone prevented the increase in collagen al (1) gene expression observed in the operated rats, thus reducing collagen content to the control level. In fibroblasts derived from abdominal adhesions, halofuginone induced dose-dependent inhibition of collagen al (1) gene expression and collagen synthesis. Collagen type Ill levels were not altered by adhesion induction or by halofuginone treatment. ConclusionsUpregulation of collagen synthesis appears to have a critical role in the pathophysiology of postoperative adhesions. Halofuginone, an inhibitor of collagen type synthesis, could be used as an important tool in understanding the role of collagen in adhesion formation, and it may become a novel and promising antifibrotic agent for preventing postoperative adhesion formation.

Pode a tela de poliéster coberta com colágeno diminuir as taxas aderências intraperitoneais na correção de hérnia incisional?

“…As a consequence, the component became exposed, which is contraindicated by the manufacturer. There were no adhesions in the center of the mesh, as described before in the literature 9,12 . The PP mesh developed 100% of the adhesion in the center.…”

Halofuginone to Prevent and Treat Thioacetamide–Induced Liver Fibrosis in Rats

“…We showed that the effect of halofuginone on collagen synthesis was transient, and on halofuginone removal, collagen gene expression in vitro 28 and in a cGvHD patient in vivo 35 returned to control levels. The reduction in the collagen ␣1(I) gene expression in rats, 32 rabbits, 27 and in chickens raised on halofuginone-containing diets for 6 weeks from hatching 45 was achieved at concentrations at which no side effects were apparent. Moreover, in all our experiments involving surgery, such as during abdominal or gynecologic adhesion formations 32,33 no abnormal wound healing was observed in the halofuginone-treated animals.…”

“…The reduction in the collagen ␣1(I) gene expression in rats, 32 rabbits, 27 and in chickens raised on halofuginone-containing diets for 6 weeks from hatching 45 was achieved at concentrations at which no side effects were apparent. Moreover, in all our experiments involving surgery, such as during abdominal or gynecologic adhesion formations 32,33 no abnormal wound healing was observed in the halofuginone-treated animals. Using the wound-tumor model in which C6 glioma spheroids were implanted in surgical incisions, acceleration in wound repair was observed in the halofuginone-treated animals.…”

“…28 In animal models in which fibrosis was induced, halofuginone prevented the increase in collagen synthesis and collagen ␣1(I) gene expression. These models included mice afflicted with cGvHD, 29 rats with pulmonary fibrosis after bleomycin treatment, 30 and rats developing adhesions after surgery in tendons, 31 the abdomen, 32 and uterine horns. 33 In liver, halofuginone prevented collagen type I gene expression in dimethylnitrosamine-induced cirrhosis in rats.…”

“…37,38 Halofuginone was given in the diet at a concentration of 5 ppm, which had previously been found to be effective in preventing abdominal and uterine horn adhesion formation in rats. 32,33 Hydroxyproline was analyzed by an amino acid analyzer after hydrolysis. 39 Preparation of Sections, In Situ Hybridization, and Immunohistochemistry.…”