Pretreatment with Warfarin Attenuates the Development of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats
| Autor: | Piotr Ceranowicz, Zygmunt Warzecha, Beata Kuśnierz-Cabala, Dawid Maduzia, Jakub Cieszkowski, Krystyna Gałązka |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Necrosis biochemical indicators acute pancreatitis Ischemia Pharmaceutical Science Vascular permeability Inflammation Pharmacology coumarin pancreatic blood flow 030226 pharmacology & pharmacy Article Analytical Chemistry lcsh:QD241-441 03 medical and health sciences 0302 clinical medicine lcsh:Organic chemistry Coumarins Edema Drug Discovery medicine Animals fibrin Rats Wistar Physical and Theoretical Chemistry Pancreas 030304 developmental biology 0303 health sciences business.industry Organic Chemistry Warfarin Anticoagulants Heparin medicine.disease Rats warfarin Pancreatitis inflammation Chemistry (miscellaneous) Reperfusion Injury Acute Disease Molecular Medicine Acute pancreatitis medicine.symptom business medicine.drug |
| Zdroj: | Molecules, Vol 25, Iss 2493, p 2493 (2020) Molecules Volume 25 Issue 11 |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules25112493 |
| Popis: | In acute pancreatitis (AP), pancreatic damage leads to local vascular injury, manifesting as endothelial damage and activation, increased vascular permeability, leukocyte rolling, sticking and transmigration to pancreatic tissue as well as activation of coagulation. Previous studies have shown that pretreatment with heparin or acenocoumarol inhibits the development of AP. The aim of the present study was to check the impact of pretreatment with warfarin, an oral vitamin K antagonist, on the development of ischemia/reperfusion-induced AP in rats. AP was induced by pancreatic ischemia followed by reperfusion of the gland. Warfarin (90, 180 or 270 µ g/kg/dose) or vehicle were administered intragastrically once a day for 7 days before induction of AP. The effect of warfarin on the severity of AP was assessed 6 h after pancreatic reperfusion. The assessment included histological, functional, and biochemical analyses. Pretreatment with warfarin given at a dose of 90 or 180 µ g/kg/dose increased the international normalized ratio and reduced morphological signs of pancreatic damage such as pancreatic edema, vacuolization of acinar cells, necrosis and the number of hemorrhages. These effects were accompanied by an improvement of pancreatic blood flow and a decrease in serum level amylase, lipase, pro-inflammatory interleukin-1&beta and plasma level of D-dimer. In contrast, pretreatment with warfarin given at a dose of 270 µ g/kg/dose led to an increase in severity of pancreatic damage and biochemical indicators of AP. In addition, this dose of warfarin resulted in deaths in some animals. Pretreatment with low doses of warfarin inhibits the development of AP induced by pancreatic ischemia followed by reperfusion. |
| Databáze: | OpenAIRE |
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