Healing effect of low doses of acenocoumarol in the course of ischemia/reperfusion-induced acute pancreatitis in rats

Warzecha, Zygmunt; Sendur, Paweł; Ceranowicz, Piotr; Bonior, Joanna; Cieszkowski, Jakub; Tomaszewska, Romana; Jaworek, Jolanta; Dembiński, Artur

doi:10.1016/j.pan.2016.05.110

Cited by 5 publications

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“…A new important finding of our current study was the discovery that treatment with acenocoumarol led to a significant decrease in the serum interleukin-1β concentration and limitation of the severity of acute pancreatitis. Moreover, this observation is in line with previous reports showing that pretreatment with acenocoumarol before the induction of acute pancreatitis reduces the pancreatitis-evoked increase in the serum level of interleukin-1β [ 19 , 20 ]. These findings taken together indicate that the acenocoumarol-induced reduction in the serum level of interleukin-1β is involved in the protective and therapeutic effect of acenocoumarol in acute pancreatitis.…”

Section: Discussionsupporting

confidence: 92%

“…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: 85%

“…Previous studies have shown that pretreatment with acenocoumarol inhibits the development of ischemia/reperfusion-, as well as, cerulein-induced acute pancreatitis [ 19 , 20 ]. However, it must be pointed out that patients with acute pancreatitis are usually seen in the hospital several hours or even days after the onset of this disease.…”

Section: Discussionmentioning

confidence: 99%

“…Saline or acenocoumarol (Acenocumarol WZF, Warszawskie Zakłady Farmaceutyczne Polfa S.A., Warsaw, Poland) were given intragastrically once daily until the day of killing the animals, which was the last day of treatment. Acenocoumarol was administered at doses of 50, 100, or 150 µg/kg/day because the earlier study [ 19 ] showed that those doses increased the international normalized ratio (INR) to a value between 2.5 and 3.5. This range of INR is recommended in most clinical situations associated with hypercoagulation [ 44 ].…”

Section: Methodsmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

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

Self Cite

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“…In a recent experimental study, pretreatment with low doses of acenocoumarol, a vitamin K antagonist, attenuated ischemia/reperfusion-induced AP and was associated with reduced leukocyte inflammatory infiltration of the pancreas as well as diminished pancreatitis-induced increase in serum IL-1β concentrations [ 198 ]. The results were confirmed in another model of experimental AP, i.e., cerulein-induced AP in rats [ 199 ].…”

Section: Therapeutic Effects Of Anticoagulants In Acute Pancreatitmentioning

confidence: 99%

The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

Dumnicka

Maduzia

Ceranowicz

et al. 2017

IJMS

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113

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Acute pancreatitis (AP) is an inflammatory disease with varied severity, ranging from mild local inflammation to severe systemic involvement resulting in substantial mortality. Early pathologic events in AP, both local and systemic, are associated with vascular derangements, including endothelial activation and injury, dysregulation of vasomotor tone, increased vascular permeability, increased leukocyte migration to tissues, and activation of coagulation. The purpose of the review was to summarize current evidence regarding the interplay between inflammation, coagulation and endothelial dysfunction in the early phase of AP. Practical aspects were emphasized: (1) we summarized available data on diagnostic usefulness of the markers of endothelial dysfunction and activated coagulation in early prediction of severe AP; (2) we reviewed in detail the results of experimental studies and clinical trials targeting coagulation-inflammation interactions in severe AP. Among laboratory tests, d-dimer and angiopoietin-2 measurements seem the most useful in early prediction of severe AP. Although most clinical trials evaluating anticoagulants in treatment of severe AP did not show benefits, they also did not show significantly increased bleeding risk. Promising results of human trials were published for low molecular weight heparin treatment. Several anticoagulants that proved beneficial in animal experiments are thus worth testing in patients.

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Analysis of biochemical parameters in an experimental model of chronic pancreatitis in rats

Bronowicka-Adamska,

Hutsch,

Szlęzak

et al. 2023

Folia Medica Cracoviensia

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Background: Despite advanced research and great progress in understanding the chronic pancreatitis (CP) pathogenesis, no current causal treatment for the condition is available. For preclinical studies, the existence of a well-characterized CP animal model is essential. The aim of the study was to assess the impact of chronic pancreatitis on the antioxidant enzymes activity in rat blood serum and on the level of glutathione (intracellular antioxidant) in rat pancreas. Methods: The experiments were carried out on the Wistar Kyoto rats in two groups: control and study group (CP), in which chemical induction of pancreatitis with dibutyl dichloride was performed. Serum enzyme activities of amylase, lipase, catalase and superoxide dismutase were analyzed. The levels of the following biochemical parameters were also investigated: total protein, albumin, calcium, magnesium, and triglycerides. Levels of low-molecular-weight thiols: reduced (GSH) and oxidized (GSSG) glutathione, were determined in pancreatic homogenates. Results: Histopathological imaging of rat pancreatic parenchyma with induced inflammation confirmed focal lymphocytic interstitial chronic pancreatitis with fibrosis features and mild parenchymal atrophy, as well as pancreatic islets degeneration. In the CP group, we observed a statistically significant decrease in serum amylase and lipase activities and in total protein/albumin levels. Also, the elevated catalase activity was registered. In CP rats’ tissues, we observed a 15-fold reduction in GSH levels. The other examined parameters remained unchanged. Clinically relevant are hypoalbuminemia and a moderate decrease in lipase activity. The described changes are most probably indicative of the impaired exocrine pancreas function, however without organ failure features.

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Healing effect of low doses of acenocoumarol in the course of ischemia/reperfusion-induced acute pancreatitis in rats

Cited by 5 publications

References 0 publications

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

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

The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

Analysis of biochemical parameters in an experimental model of chronic pancreatitis in rats

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