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

Abstract

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. 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. 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). Halofuginone was found to be effective in reducing SHOP-related inflammation, acinar atrophy, and fibrosis in the pancreas.