Pretreatment with Warfarin Attenuates the Development of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats

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.

Protective effect of bergapten in acetic acid-induced colitis in rats

“…Prior studies conducted in the gut have shown that acenocoumarol, inhibits the development of acute pancreatitis [ 48 , 49 ] and enhances recovery in this disease [ 50 ]. Maduzia et al., (2020) [ 51 ], in their study also showed a similar protective effect exhibited by warfarin treatment before the induction of acute pancreatitis in the model employed in the study. Anti-inflammatory, protective and therapeutic effects have been observed in other studies on colons on the administration of coumarins such as daphnetin [ 52 ], 4-methylesculin [ 53 ], or osthole [ 54 ].…”

Association of Platelets and White Blood Cells Subtypes with Trauma Patients’ Mortality Outcome in the Intensive Care Unit

“…Damage to the gastric mucosa is associated with a decrease in blood flow through the gastric mucosa [26], whereas the protection and healing of gastric mucosa is associated with an increase in gastric blood flow [27][28][29]. A similar effect of blood flow organ integrity was observed in other organs of the digestive system such as the duodenum [30], colon [31], liver [31] and pancreas [32]. Disturbances to pancreatic blood flow and pancreatic ischemia play an essential role in the development of acute pancreatitis in different clinical settings [33], including hypovolemic shock [34].…”

Luzhou‐Feier powder reduces inflammatory response and improves intestinal immune barrier in rats with severe acute pancreatitis

“…However, osmotic diarrhea caused by enteral nutrition was ignored. Osmotic diarrhea leads to hypovolemia which can disrupt therapy may bring some benefits (Maduzia et al, 2020). However, there may be some risks and side effects, and further research in this field is needed.…”