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Title: Influence of exogenous obestatin on the development and course of acute edematous pancreatitis

Abstract:

Obestatin is a peptide derived from the same gene as ghrelin. Obestatin, as a ghrelin, has been originally extracted from rat stomach, and the stomach seems to be a major source of endogenous obestatin. Previous studies have shown that ghrelin exhibits protective and therapeutic effect in the pancreas. Administration of ghrelin inhibits the development of acute pancreatitis and accelerates pancreatic recovery in the course of this disease. Recent study has shown that obestatin promotes survival of isolated human pancreatic cells and β-cells, as well as improves the generation of functional β-cells in vitro from mouse pancreatic islet-derived precursor cells.Aim of the present study was to investigate the influence of obestatin administration on the development and course of cerulein-induced acute edematous pancreatitis.Methods: Studies were performed in two separate series on male Wistar rats. In both series of studies, acute pancreatitis was induced by five intraperitoneal injection of cerulein (given at the dose of 50 μg/kg/dose) with 1-h intervals between injections.The first series of studies were performed to examine the effect of obestatin administration on the development of acute pancreatitis. Obestatin was given twice (30 min prior to the first injection of cerulein, and 3 h later) at the dose of 4, 8 or 16 nmol/kg/dose. This series of studies was ended 1 h after the last dose of cerulein.The second series of studies were performed to evaluate the effect of obestatin administration on the course of acute pancreatitis. Obestatin was administered twice a day at the dose of 8 nmol/kg/dose; starting the first dose 24 h after the last injection of cerulein. Severity of acute pancreatitis was examined 1 h after the last dose of cerulein or after 1, 2, 3, 5, 7 or 10 days after the last injection of cerulein. ; Results: The first series of studies has shown that morphological features of pancreases obtained from animals treated with obestatin before induction of acute pancreatitis, exhibit the decrease in pancreatic edema, pancreatic leukocyte infiltration and vacuolization of acinar cells. These effects have been accompanied by a reduction in the pancreatitis-evoked increase in serum level of pancreatic digestive enzymes, lipase amylase and poly-C ribonuclease. Also serum concentration of pro-inflammatory interleukin-1β was decreased. The pancreatitis-evoked decrease in pancreatic blood flow and pancreatic DNA synthesis was partially reversed.The second series of study has shown that administration of cerulein has led to the development of acute oedematous pancreatitis in all rats and maximal severity of this disease was observed 24 h after the last dose of cerulein. Treatment with obestatin reduced morphological signs of pancreatic damage such as pancreatic edema, leukocyte infiltration and vacuolization of acinar cells, and led to earlier regeneration of the pancreas. Biochemical indexes of the severity of pancreatitis, such as serum activity of lipase and amylase were significantly reduced in animals treated with obestatin. These effects were associated with an increase in pancreatic DNA synthesis and a decrease in serum level of pro-inflammatory interleukin-1β. Administration of obestatin has improved pancreatic blood flow in rats with acute pancreatitis.Conclusions: (1) Obestatin exhibits protective and therapeutic effect in the pancreas. (2) Administration of obestatin before and during the induction of acute pancreatitis inhibits the development of this inflammation. (3) Administration of exogenous obestatin after induction of acute pancreatitis reduces severity of acute pancreatitis and accelerates pancreatic recovery in this disease. (4) These beneficial effects of obestatin administration are related, at least in part, to the improvement of pancreatic blood flow and pancreatic cell vitality, as well as to reduction in the release of pro-inflammatory interleukin-1β.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

choroby układu trawiennego

Degree grantor:

Uniwersytet Jagielloński. Collegium Medicum. Wydział Lekarski.

Promoter:

Artur Dembiński

Date issued:

2013

Format:

application/pdf

Identifier:

oai:dl.cm-uj.krakow.pl:3933

Call number:

ZB-121447

ControlNumberVIRTUA:

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Language:

pol

Access rights:

tylko w bibliotece

Location of original object:

Biblioteka Medyczna Uniwersytetu Jagiellońskiego- Collegium Medicum

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Last modified:

Jun 26, 2019

In our library since:

Nov 26, 2014

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3

All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/3933

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ZB-121447 Jun 26, 2019
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