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

Zygmunt Warzecha,Piotr Ceranowicz,Artur Dembiński,Romana Tomaszewska,Rafał Olszanecki,Paweł Sendur,Jakub Cieszkowski,Marcin Dembiński,Beata Kuśnierz-Cabala,Tadeusz Ambroży

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.

Highlights

There is close bidirectional relationship between coagulation and inflammation [1,2]
Mild Acute pancreatitis (AP) is associated with scattered intravascular thrombosis, whereas severe AP may lead to the development of disseminated intravascular coagulation [6,7,8,9]
Serum activity of lipase (Figure 6) and amylase (Figure 7), serum concentrations of interleukin-1β (IL-1β) (Figure 8), and plasma D-dimer concentration (Figure 9) were not affected by acenocoumarol given in rats without causing pancreatitis

Summary

Introduction

There is close bidirectional relationship between coagulation and inflammation [1,2]. Inflammation can be both a cause and a result of induction of coagulation [1,2,3,4]. Acute pancreatitis (AP) is associated with coagulative disorders [6,7,8,9]. The stage of these disorders depends on the severity of AP. Mild AP is associated with scattered intravascular thrombosis, whereas severe AP may lead to the development of disseminated intravascular coagulation [6,7,8,9]. Measurement of disseminated intravascular coagulation parameters is useful in the assessment of AP severity and prediction for poor outcome of this disease at admission [7,8]

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Conclusion