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

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

doi:10.3390/ijms17101709

Cited by 23 publications

(28 citation statements)

References 49 publications

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“…Acute pancreatitis stimulates intravascular coagulation with formation of thrombi within blood vessels and coagulation disorders may be in the range between scattered intravascular thrombosis in pancreatic microcirculation to severe disseminated intravascular coagulation [ 84 ]. Moreover, animals and clinical studies showed that treatment with heparin or anticoagulants inhibits the development of acute pancreatitis and accelerates the recovery in this disease [ 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 ]. These findings indicate that disorders of coagulation play the important role in acute pancreatitis and these disorders may be responsible for the lack of significant improvement in pancreatic blood flow in animals treated with ghrelin despite improved histology of the pancreas.…”

Section: Discussionmentioning

confidence: 99%

Capsaicin-Sensitive Sensory Nerves Are Necessary for the Protective Effect of Ghrelin in Cerulein-Induced Acute Pancreatitis in Rats

Bonior

Warzecha

Ceranowicz

et al. 2017

IJMS

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Ghrelin was shown to exhibit protective and therapeutic effect in the gut. Aim of the study was to investigate the role of sensory nerves (SN) in the protective effect of ghrelin in acute pancreatitis (AP). Studies were performed on male Wistar rats or isolated pancreatic acinar cells. After capsaicin deactivation of sensory nerves (CDSN) or treatment with saline, rats were pretreated intraperitoneally with ghrelin or saline. In those rats, AP was induced by cerulein or pancreases were used for isolation of pancreatic acinar cells. Pancreatic acinar cells were incubated in cerulein-free or cerulein containing solution. In rats with intact SN, pretreatment with ghrelin led to a reversal of the cerulein-induced increase in pancreatic weight, plasma activity of lipase and plasma concentration of tumor necrosis factor-α (TNF-α). These effects were associated with an increase in plasma interleukin-4 concentration and reduction in histological signs of pancreatic damage. CDSN tended to increase the severity of AP and abolished the protective effect of ghrelin. Exposure of pancreatic acinar cells to cerulein led to increase in cellular expression of mRNA for TNF-α and cellular synthesis of this cytokine. Pretreatment with ghrelin reduced this alteration, but this effect was only observed in acinar cells obtained from rats with intact SN. Moreover, CDSN inhibited the cerulein- and ghrelin-induced increase in gene expression and synthesis of heat shock protein 70 (HSP70) in those cells. Ghrelin exhibits the protective effect in cerulein-induced AP on the organ and pancreatic acinar cell level. Sensory nerves ablation abolishes this effect.

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Section: Discussionmentioning

confidence: 99%

Capsaicin-Sensitive Sensory Nerves Are Necessary for the Protective Effect of Ghrelin in Cerulein-Induced Acute Pancreatitis in Rats

Bonior

Warzecha

Ceranowicz

et al. 2017

IJMS

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“…In harmony with those findings is the observation that the inhibition of coagulation by pretreatment with low doses of acenocoumarol, a vitamin K antagonist, exhibits a protective effect on the pancreas and inhibits the development of acute pancreatitis induced by ischemia/reperfusion [19] or cerulein [20]. However, from a clinical point of view, it is more important to determine whether the administration of acenocoumarol after the development of acute pancreatitis exhibits any therapeutic effect on this disease.…”

Section: Introductionmentioning

confidence: 94%

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

Warzecha

Sendur

Ceranowicz

et al. 2017

IJMS

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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.

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“…Moreover, the treatment with acenocoumarol improved pancreatic blood flow [ 26 ]. These observations were further confirmed in a rodent model of rats with cerulean-induced AP [ 27 ]. Surprisingly, acenocoumarol seems to be effective not only in AP management, but even in the prevention of disease.…”

Section: Discussionmentioning

confidence: 63%

Plasma Sphingolipids in Acute Pancreatitis

Konończuk

Łukaszuk

Żendzian-Piotrowska

et al. 2017

IJMS

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Acute pancreatitis (AP) is a prevalent gastrointestinal disorder associated with systemic inflammatory response syndrome and, in the case of severe AP, a mortality rate ranging from 36% to 50%. Standard clinical treatment of AP includes intensive hydration, analgesia, and management of complications. Unfortunately, the direct treatment of AP at the level of its molecular pathomechanism has not yet been established. Recent studies indicate that the sphingolipid signaling pathway may be one of the important factors contributing to the development of inflammation in pancreatic diseases. In the current study, we sought to investigate this promising route. We examined the plasma sphingolipid profile of 44 patients with acute pancreatitis, dividing them into three groups: mild, moderate and severe AP. Samples were collected from these groups at days 1, 3 and 7 following their hospital admission. We demonstrated significant changes in blood plasma sphingolipids in relation to the time course of AP. We also found an inhibition of de novo ceramide synthesis in mild and moderate AP. However, the most important and novel finding was a significant elevation in sphingosine-1-phosphate (S1P) (a downstream metabolite of ceramide) in mild AP, as well as a dramatic reduction in the lipid molecule content in the early stage (days 1 and 3) of severe AP. This strongly indicates that plasma S1P could serve as a prognostic marker of AP severity.

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

Cited by 23 publications

References 49 publications

Capsaicin-Sensitive Sensory Nerves Are Necessary for the Protective Effect of Ghrelin in Cerulein-Induced Acute Pancreatitis in Rats

Capsaicin-Sensitive Sensory Nerves Are Necessary for the Protective Effect of Ghrelin in Cerulein-Induced Acute Pancreatitis in Rats

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

Plasma Sphingolipids in Acute Pancreatitis

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