Therapeutic Effect of Obestatin in the Course of Cerulein-Induced Acute Pancreatitis

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Abstract
Objective The aim of this study was to determine the impact of obestatin therapy on the course of cerulein-induced pancreatitis. Methods Acute pancreatitis was induced by cerulein given intraperitoneally 5 times with 1 hour intervals at the dose of 50 μg/kg per dose. Obestatin was administered twice a day at the dose of 8 nmol/kg per dose, starting the first dose 24 hours after the last injection of cerulein. Severity of acute pancreatitis (AP) was examined at 0 hour or 1, 2, 3, 5, 7, and 10 days after the last injection of cerulein. Results Administration of cerulein led to development of acute edematous pancreatitis in all rats, and maximal severity of this disease was observed 24 hours after induction of pancreatitis. Treatment with obestatin reduced morphological signs of pancreatic damage (pancreatic edema, leukocyte infiltration, vacuolization of acinar cells) and led to earlier regeneration of the pancreas. Biochemical indexes of severity of pancreatitis such as serum activity of pancreatic digestive enzymes were significantly reduced in animals treated with obestatin. These effects were accompanied by increase in pancreatic DNA synthesis and decrease in serum level of proinflammatory interleukin 1β. In addition, administration of obestatin improved pancreatic blood flow in rats with AP. Conclusions Treatment with exogenous obestatin reduces severity of AP and accelerates pancreatic recovery.

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