Halofuginone, an inhibitor of collagen type I synthesis, prevents postoperative adhesion formation in the rat uterine horn model☆,☆☆,★
Section snippets
Materials
[2,3,4,5 3H]L-proline (122 Ci/mmol) was obtained from the Radiochemical Centre (Amersham, United Kingdom). Highly purified Clostridium histolyticum collagenase type VII free of nonspecific proteases, β-aminopropionitrile, Dulbecco’s modified Eagle’s medium, and trypsin–ethylenediaminetetra-acetic acid solution (0.25% and 0.02%, respectively) were obtained from Sigma (St. Louis, Mo). Fetal calf serum was obtained from Biochemical Industries (Bet-HaEmek, Israel). Sirius red F3B was obtained from
Effect of halofuginone on uterine horn adhesions
Three experiments were performed to evaluate the effects of halofuginone on the number and severity of rat uterine horn adhesions. In the first experiment adhesions were induced and halofuginone was given by intraperitoneal injection at a concentration of 40 μg/kg body weight every other day starting 1 week before operation (Table I).No adhesions were observed in the control, nonoperated, rats with or without halofuginone. All rats that underwent the operation procedures but did not receive
Comment
Postoperative pregnancy rates decline as a result of peritubular adhesions. In addition, adhesions may cause intestinal obstruction and chronic pelvic pain, especially during ovulation. The involvement of fibroblast proliferation and extracellular matrix deposition—especially collagen—in scar formation in general,19 and in adhesion formation in particular,14, 20 is well documented. Up-regulation of collagen type I synthesis appears to play a critical role in the pathophysiologic mechanism of
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Cited by (48)
Effectiveness of hyaluronic acid/carboxymethylcellulose in preventing adhesive bowel obstruction after laparoscopic radical cystectomy
2019, Asian Journal of SurgeryCitation Excerpt :If fibrinolysis is impaired, however, adhesions are induced by organization of fibrin and deposition of collagen.19 Six methods to prevent postoperative adhesion have been described: minimizing peritoneal damage by using minimally invasive surgical techniques,21 preventing fibrin formation with heparin or adenosine,22 preventing inflammatory reactions with steroids or nonsteroidal anti-inflammatory medications,23 promoting fibrinolysis with streptokinase or urokinase,24 preventing fibrin organization and collagen deposition with halofuginone,25 and separating damaged surfaces.26 The abdominal cavity contains several natural barriers, including the peritoneum, omentum, and amnion.27
The chemistry and biology of febrifugine and halofuginone
2014, Bioorganic and Medicinal ChemistryCitation Excerpt :Thus, it was suggested that halofuginone is a new type of ATP-dependent inhibitor that simultaneously occupies two different substrate binding sites on human prolyl-transfer RNA synthetase.84 These results indicate a possible similar mechanism of action for febrifugine in the context of its antimalarial activity.85 Notably, only the 2R,3S isomer of halofuginone, which matches the absolute configuration of febrifugine, exhibits biological activity.
Halofuginone infused keratin hydrogel attenuates adhesions in a rodent cecal abrasion model
2012, Journal of Surgical ResearchCitation Excerpt :The long-lasting release characteristics are ideal in adhesion prevention because the mesothelial cell proliferation or reperitonealization process continues for 7 to 10 d following the tissue damage and corresponds to progressive fibrosis and development of adhesions [7]. The release assay suggests that the maximum HF release rate from keratin-HF hydrogel is 1.24 μg/d, which is an exceptionally small daily dose when reviewing other studies examining the possibility of using HF as an anti-adhesion drug [12,13]. This low daily release dose and the limited 2-wk follow-up period may have contributed to lack of complete adhesion prevention.
Pathogenesis and Clinical and Economic Consequences of Postoperative Ileus
2012, Surgical Clinics of North AmericaEffects of contractubex on the prevention of postoperative peritoneal adhesion
2010, Journal of Surgical ResearchCitation Excerpt :In the literature there are some important examples of this approach. For example, Halofuginone, a specific inhibitor of collagen type I synthesis, was found to significantly lower the PPAs formed using two types of adhesion induction, cecum scraping and uterine horn scraping [33, 34]. In the cited studies, however, Halofuginone was applied daily, either intraperitoneally or orally.
Medical Application of Hyaluronan
2004, Chemistry and Biology of Hyaluronan
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Supported by Collgard Biopharmaceuticals Ltd, Tel Aviv, Israel. Contribution No. 2337-E, 1997 series, from the Agricultural Research Organization, The Volcani Center, Bet Dagan, Israel.
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Reprint requests: Mark Pines, PhD, Institute of Animal Science, ARO, The Volcani Center, Bet Dagan 50250, Israel.
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0002-9378/99 $8.00 + 06/1/95569