The effect of halofuginone, a specific inhibitor of collagen type 1 synthesis, in the prevention of pancreatic fibrosis in an experimental model of severe hyperstimulation and obstruction pancreatitis |
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Authors: | Karatas Adem Paksoy Melih Erzin Yusuf Carkman Sinan Gonenc Murat Ayan Fadil Aydogan Fatih Uzun Hafize Durak Haydar |
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Affiliation: | Department of General Surgery, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey. drade_mail@yahoo.com |
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Abstract: | BACKGROUND: The aim of this paper is to assess the effects of halofuginone, a specific inhibitor of synthesis of collagen Type 1, on fibrogenetic process in an experimental model of early pancreatic fibrosis. METHODS: Thirty rats were divided into three equal groups: group 1, sham laparotomy; group 2, severe hyperstimulation and obstruction pancreatitis (SHOP) with no treatment; group 3, SHOP with halofuginone treatment group. SHOP model was induced by complete pancreatic duct obstruction and daily cerulein hyperstimulation (50 microg/kg, intraperitoneally). Halofuginone was administered daily from the operative day (5 mg/kg, intraperitoneally). All of the animals were sacrificed, and blood and pancreatic tissue samples were obtained for biochemical and histopathological examination on the 5th postoperative day. RESULTS: No mortality was observed in any group. Serum amylase, lipase, hyaluronic acid, and nitric oxide levels were significantly higher in groups 2 and 3 compared with group 1 (P < 0.05), but were significantly lower in group 3 compared with group 2 (P < 0.05). No significant differences were observed regarding serum malondialdehyde and glutathione levels between groups 1 and 3. Tissue hydroxyproline levels were found to be significantly higher in groups 2 and 3 compared with group 1 (P < 0.001), but were significantly lower in group 3 compared with group 2 (P < 0.001). Although tissue hydroxyproline levels were significantly higher in the halofuginone treatment group compared with the control group, histopathological evaluation did not reveal a significant difference between these groups regarding collagen deposition. When group 3 was compared with group 2, halofuginone significantly reduced inflammation and acinar atrophy in the pancreas as well (P < 0.05). CONCLUSION: Halofuginone was found to be effective in reducing SHOP-related inflammation, acinar atrophy, and fibrosis in the pancreas. |
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Keywords: | halofuginone chronic pancreatitis SHOP model pancreatic fibrosis |
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