title: Electron-microscopic evidence of mitochondriae containing macroautophagy in experimental acute pancreatitis: implications for cell death.
abstract: BACKGROUND
  Dysfunctional autophagy and necrosis are characteristic features of severe acute pancreatitis.
  
  
  OBJECTIVE
  To unravel the cellular mechanisms underlying the pathogenesis of acute pancreatitis.
  
  
  METHODS
  We studied the ultrastructural pancreatic morphology using electron microscopy in experimental acute pancreatitis. The control group of animals received intraperitoneal injections of normal saline. Different severity of acute pancreatitis was induced by low and high doses of caerulein in Swiss albino mice. In the low dose group, pancreatitis was induced by 4 injections of caerulein given hourly [50 μg/kg/dose - total of 200 μg/kg] and in the high dose group by 8 injections given hourly (total of 400 μg/kg). The experiments were repeated in Na-taurocholate model of acute pancreatitis in rats. The pancreatic tissue was processed and studied by transmission electron microscopy for ultrastructural changes.
  
  
  RESULTS
  The acinar cells of the pancreatitis animals revealed autophagosomes that contained cellular organelles, including mitochondria. The animals that received a higher dose of caerulein had numerous cells showing a necrotic morphology, whereas the animals in the low dose group showed a predominantly apoptotic cell morphology. The Na-taurocholate model in rats also showed similar features of severe pancreatitis with cellular necrosis and macroautophagy.
  
  
  CONCLUSIONS
  Dysfunctional mitochondria in the injured pancreatic acinar cells are degraded by macroautophagy. These observations are not model specific. Mitochondrial dysfunction and consequent energy deficit in the cells might be causally related to cellular necrosis.
authors.affiliation: Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Tony George
authors.initials: TG
authors.lastname: Jacob
authors.affiliation: Department of Gastrointestinal Surgery, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Vipin Iyani
authors.initials: VI
authors.lastname: Sreekumar
authors.affiliation: Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Tara Sankar
authors.initials: TS
authors.lastname: Roy
authors.affiliation: Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi 110029, India. Electronic address: pkgarg@aiims.ac.in.
authors.forename: Pramod Kumar
authors.initials: PK
authors.lastname: Garg
mesh_terms: D000818:Animals; D001343:Autophagy; D016923:Cell Death; D002108:Ceruletide; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000473:pathology* / Q000648:ultrastructure; D009336:Necrosis; D010179:Pancreas / Q000473:pathology / Q000648:ultrastructure; D010195:Pancreatitis / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid
chemical_list: D013656:Taurocholic Acid; D002108:Ceruletide
keywords: Acute pancreatitis; Autophagy; Caerulein; Electron microscopy; Mitochondria; Necrosis