Pretreatment with obestatin reduces the severity of ischemia/reperfusion-induced acute pancreatitis in rats

Obestatin, as ghrelin, has been originally extracted from the stomach, which remains its major source. Previous studies have shown that administration of obestatin exhibits protective and healing-promoting effects in several organs, including the stomach and kidney. In pancreas, pretreatment with obestatin inhibits the development of cerulein-induced acute pancreatitis and promotes survival of pancreatic beta cells and human islets. The aim of the present study was to check the universality of protective effect of obestatin in the pancreas. For this reason we investigated the influence of obestatin administration on the development of ischemia/reperfusion-induced pancreatitis. Acute pancreatitis was induced by pancreatic ischemia followed by reperfusion of the gland. Obestatin (4, 8 or 16 nmol/kg/dose) was administered intraperitoneally twice: 0.5 h before exposure to ischemia, and 3 h after the first injection. The effect of obestatin on the course of necrotizing pancreatitis was assessed after 6-h reperfusion, and included histological, functional, and biochemical analyses. Treatment with obestatin reduced morphological signs of pancreatic damage including edema, vacuolization of acinar cells, hemorrhages, acinar necrosis, and leukocyte infiltration of the gland. These effects were accompanied by an improvement of pancreatic DNA synthesis and superoxide dismutase activity, and a decrease in serum level of lipase and pro-inflammatory interleukin-1β. Moreover pretreatment with obestatin reduced myeloperoxidase activity and malondialdehyde concentration in pancreatic tissue of rats with acute pancreatitis. Conclusions: Administration of obestatin inhibits the development of ischemia/reperfusion-induced acute pancreatitis. This observation, taken together with previous findings that obestatin protects the pancreas against cerulein-induced pancreatitis, indicates that protective effect of obestatin in the pancreas is universal and independent of the primary cause of acute pancreatitis.