Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

Abstract

Intravascular activation of coagulation is observed in acute pancreatitis and is related to the severity of this inflammation. The aim of our study was to evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis induced in male rats by pancreatic ischemia followed by reperfusion. Acenocoumarol at a dose of 50, 100, or 150 µg/kg/dose was administered intragastrically once a day, starting the first dose 24 h after the initiation of pancreatic reperfusion.

RESULTS:

Histological examination showed that treatment with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats with pancreatitis. Moreover, the administration of acenocoumarol decreased pancreatic inflammatory infiltration and vacuolization of pancreatic acinar cells. These findings were accompanied with a reduction in the serum activity of lipase and amylase, concentration of interleukin-1β, and plasma d-Dimer concentration. Moreover, the administration of acenocoumarol improved pancreatic blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150 µg/kg/dose was the most effective in the treatment of early phase acute pancreatitis. However later, acenocoumarol given at the highest dose failed to exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still effective in the treatment of acute pancreatitis.

CONCLUSION:

Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats.

• Authors: Zygmunt Warzecha, Paweł Sendur, Piotr Ceranowicz, Jakub Cieszkowski, Marcin Dembiński, Ryszard Sendur, Joanna Bonior, Jolanta Jaworek, Tadeusz Ambroży, Rafał Olszanecki, Beata Kuśnierz-Cabala, Kaczmarzyk Tomasz, Romana Tomaszewska, Artur Dembiński
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 18 Issue 4 (Apr 21 2017) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 28430136 (Publication Type: Journal Article)

Chemical References

• Fibrin Fibrinogen Degradation Products
• Interleukin-1beta
• fibrin fragment D
• DNA
• Lipase
• Amylases
• Acenocoumarol

Topics

• Acenocoumarol (pharmacology, therapeutic use)
• Acute Disease
• Amylases (blood)
• Animals
• DNA (metabolism)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Fibrin Fibrinogen Degradation Products (analysis)
• Interleukin-1beta (blood)
• International Normalized Ratio
• Lipase (blood)
• Male
• Pancreas (blood supply, drug effects, metabolism)
• Pancreatitis (drug therapy, etiology, pathology)
• Rats
• Rats, Wistar
• Regional Blood Flow
• Reperfusion Injury (complications, pathology)
• Severity of Illness Index