title: Obestatin Accelerates the Recovery in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.
abstract: OBJECTIVE
  Several previous studies have shown that obestatin exhibits protective and regenerative effects in some organs including the stomach, kidney, and the brain. In the pancreas, pretreatment with obestatin inhibits the development of cerulein-induced acute pancreatitis, and promotes survival of pancreatic beta cells and human islets. However, no studies investigated the effect of obestatin administration following the onset of experimental acute pancreatitis.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the impact of obestatin therapy in the course of ischemia/reperfusion-induced pancreatitis. Moreover, we tested the influence of ischemia/reperfusion-induced acute pancreatitis and administration of obestatin on daily food intake and pancreatic exocrine secretion.
  
  
  METHODS
  Acute pancreatitis was induced by pancreatic ischemia followed by reperfusion of the pancreas. Obestatin (8 nmol/kg/dose) was administered intraperitoneally twice a day, starting 24 hours after the beginning of reperfusion. The effect of obestatin in the course of necrotizing pancreatitis was assessed between 2 and 14 days, and included histological, functional, and biochemical analyses. Secretory studies were performed on the third day after sham-operation or induction of acute pancreatitis in conscious rats equipped with chronic pancreatic fistula.
  
  
  RESULTS
  Treatment with obestatin ameliorated morphological signs of pancreatic damage including edema, vacuolization of acinar cells, hemorrhages, acinar necrosis, and leukocyte infiltration of the gland, and led to earlier pancreatic regeneration. Structural changes were accompanied by biochemical and functional improvements manifested by accelerated normalization of interleukin-1β level and activity of myeloperoxidase and lipase, attenuation of the decrease in pancreatic DNA synthesis, and by an improvement of pancreatic blood flow. Induction of acute pancreatitis by pancreatic ischemia followed by reperfusion significantly decreased daily food intake and pancreatic exocrine secretion. Administration of obestatin at doses used was without significant effect with regard to daily food intake or pancreatic exocrine secretion in sham-operated rats, as well as in rats with acute pancreatitis. On the other hand, obestatin abolished a statistical significance of difference in food intake between animals with AP and control animals without pancreatic fistula and induction of AP.
  
  
  CONCLUSIONS
  Treatment with the exogenous obestatin reduces severity of ischemia/reperfusion-induced acute pancreatitis and accelerates recovery in this disease. The involved mechanisms are likely to be multifactorial, and are mediated, at least in part, by anti-inflammatory properties of obestatin.
authors.affiliation: Department of Endocrinology and Diabetes Mellitus, Northumbria NHS Foundation Trust, Rake Lane, North Shields, Tyne and Wear, United Kingdom.
authors.forename: Jakub
authors.initials: J
authors.lastname: Bukowczan
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Zygmunt
authors.initials: Z
authors.lastname: Warzecha
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ceranowicz
authors.affiliation: Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Kuśnierz-Cabala
authors.affiliation: Department of Pathology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Romana
authors.initials: R
authors.lastname: Tomaszewska
mesh_terms: D000208:Acute Disease; D000818:Animals; D004365:Drugs, Chinese Herbal; D004435:Eating / Q000187:drug effects; D054439:Ghrelin / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000097:blood; D007511:Ischemia / Q000150:complications; D008049:Lipase / Q000097:blood; D008297:Male; D010179:Pancreas / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010195:Pancreatitis / Q000188:drug therapy / Q000209:etiology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications* / Q000188:drug therapy
chemical_list: D004365:Drugs, Chinese Herbal; D054439:Ghrelin; D053583:Interleukin-1beta; C530779:Myelophil; D008049:Lipase