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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.
Karatas, Adem; Paksoy, Melih; Erzin, Yusuf; Carkman, Sinan; Gonenc, Murat; Ayan, Fadil; Aydogan, Fatih; Uzun, Hafize; Durak, Haydar.
Afiliação
  • Karatas A; Department of General Surgery, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey. drade_mail@yahoo.com
J Surg Res ; 148(1): 7-12, 2008 Jul.
Article em En | MEDLINE | ID: mdl-18570924
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pâncreas / Piperidinas / Inibidores da Síntese de Proteínas / Colágeno Tipo I / Quinazolinonas Limite: Animals Idioma: En Revista: J Surg Res Ano de publicação: 2008 Tipo de documento: Article País de afiliação: Turquia País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pâncreas / Piperidinas / Inibidores da Síntese de Proteínas / Colágeno Tipo I / Quinazolinonas Limite: Animals Idioma: En Revista: J Surg Res Ano de publicação: 2008 Tipo de documento: Article País de afiliação: Turquia País de publicação: Estados Unidos