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Treatment with ghrelin attenuates the development of ischemia/reperfusion - induced pancreatitis

Piotr Ceranowicz, Zygmunt Warzecha, Artur Dembiński, Jakub Cieszkowski, Katarzyna Wiech, Wiesław W Pawlik, Romana Tomaszewska, Beata Kuśnierz-Cabała, Jerzy W Naskalski, Atsukazu Kuwahara, Ikuo Kato

Med Sci Tech 2005; 46(4): RA51-55

ID: 881474

Available online:

Published: 2005-07-16


Background: Ghrelin is a 28 amino acid peptide primary isolated from the rat stomach. It stimulates growth hormone secretion, food intake and exhibits gastroprotective properties. The presence of ghrelin and its receptor was found in different organs, including the pancreas. Aim of study was to investigate the influence of ghrelin administration on the development of acute ischemia/reperfusion-induced pancreatitis. Material i Methods: Acute pancreatitis was evoked in rat by clamping of inferior splenic artery for 30 min followed by reperfusion. Ghrelin was administered twice (30 min prior to start of ischemia and after next 3 h) at the doses: 4, 8 or 16 nmol/kg/dose. After 6-h reperfusion animals were anesthetized and the following parameters were measured: pancreatic blood flow, pancreatic DNA synthesis, serum lipase and poly-C ribonuclease activity, serum interleukin-1 (IL-1), interleukin-10 (IL-10), growth hormone (GH) and insulin-like growth factor-1 (IGF-1) concentration and morphological signs of pancreatitis. Results: Treatment with ghrelin attenuated the development of ischemia/reperfusion-induced pancreatitis, what was demonstrated in histological examination as the reduction in pancreatic edema, inflammatory infiltration, necrosis, hemorrhages and the decrease in vacuolization of pancreaticacinar cells. Also, ghrelin administration decreased the activity of lipase and poly-C ribonuclease, and concentration of pro-inflammatory IL-1 in the serum, whereas the pancreatitis-evoked fall in pancreatic DNA synthesis was partly reversed. Treatment with ghrelin was without effect on the pancreatitis-related fall of pancreatic blood flow. Ischemia/reperfusion--induced pancreatitis strongly reduced serum concentration of GH and IGF-1, and ghrelin administration reversed this effect. Ghrelin at the dose 8 nmol/kg exhibited maximal beneficial effect. Conclusions: Treatment with ghrelin inhibits the development of ischemia/reperfusion-induced pancreatitis. Protective effect of ghrelin seems to be related to reduction in inflammatory infiltration of pancreatic tissue, inhibition of the release of pro-inflammatory IL-1 and restoration of IGF-1 level to control value. (Clin. Exp. Med. Lett. 2005; 46(4):51-55)

Keywords: acute pancreatitis, Ghrelin, interleukin-1β, insulin-like growth factor-1 (IGF-10)



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