Abstract
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 µg/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 µg/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-1β and plasma level of D-dimer. In contrast, pretreatment with warfarin given at a dose of 270 µg/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.
Highlights
Coagulation and inflammation show a close relationship based on positive feedback
Our study showed that pretreatment with low doses of warfarin inhibits the development of acute pancreatitis (AP) evoked by pancreatic ischemia followed by reperfusion
We originally used 80 rats, but three rats died on the third day of pretreatment with warfarin given at a dose of 270 μg/kg/dose without induction of acute pancreatitis (AP)
Summary
Coagulation and inflammation show a close relationship based on positive feedback. Inflammation leads to activation of coagulation, which stimulates the development of inflammation [1,2].Pro-inflammatory cytokines play an important role in the activation of coagulation cascade leading to the formation of fibrin. Coagulation and inflammation show a close relationship based on positive feedback. Inflammation leads to activation of coagulation, which stimulates the development of inflammation [1,2]. Pro-inflammatory cytokines play an important role in the activation of coagulation cascade leading to the formation of fibrin. This effect is associated, among others, with the overexpression of Molecules 2020, 25, 2493; doi:10.3390/molecules25112493 www.mdpi.com/journal/molecules. Apart from the promotion of clot formation, inflammation leads to the reduction in the activity of anticoagulant mechanisms and inhibits fibrinolysis [3,5]. Infection and inflammation lead to activation of coagulation and in severe cases may lead to disseminated intravascular coagulation (DIC) [4]
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