Protective Effect of Pretreatment with Acenocoumarol in Cerulein-Induced Acute Pancreatitis

Int J Mol Sci. 2016 Oct 12;17(10):1709. doi: 10.3390/ijms17101709.

Abstract

Coagulation is recognized as a key player in inflammatory and autoimmune diseases. The aim of the current research was to examine the effect of pretreatment with acenocoumarol on the development of acute pancreatitis (AP) evoked by cerulein.

Methods: AP was induced in rats by cerulein administered intraperitoneally. Acenocoumarol (50, 100 or 150 µg/kg/dose/day) or saline were given once daily for seven days before AP induction.

Results: In rats with AP, pretreatment with acenocoumarol administered at the dose of 50 or 100 µg/kg/dose/day improved pancreatic histology, reducing the degree of edema and inflammatory infiltration, and vacuolization of acinar cells. Moreover, pretreatment with acenocoumarol given at the dose of 50 or 100 µg/kg/dose/day reduced the AP-evoked increase in pancreatic weight, serum activity of amylase and lipase, and serum concentration of pro-inflammatory interleukin-1β, as well as ameliorated pancreatic DNA synthesis and pancreatic blood flow. In contrast, acenocoumarol given at the dose of 150 μg/kg/dose did not exhibit any protective effect against cerulein-induced pancreatitis.

Conclusion: Low doses of acenocoumarol, given before induction of AP by cerulein, inhibit the development of that inflammation.

Keywords: acute pancreatitis; coagulation; inflammation; interleukin-1β; lipase.

MeSH terms

  • Acenocoumarol / pharmacology*
  • Animals
  • Anticoagulants / pharmacology
  • Ceruletide*
  • Dose-Response Relationship, Drug
  • Lipase / blood
  • Male
  • Organ Size / drug effects
  • Pancreas / drug effects*
  • Pancreas / pathology
  • Pancreatitis / chemically induced*
  • Pancreatitis / prevention & control*
  • Rats

Substances

  • Anticoagulants
  • Ceruletide
  • Lipase
  • Acenocoumarol