title: The crucial role of early mitochondrial injury in L-lysine-induced acute pancreatitis.
abstract: OBJECTIVE
  Large doses of intraperitoneally injected basic amino acids, L-arginine, or L-ornithine, induce acute pancreatitis in rodents, although the mechanisms mediating pancreatic toxicity remain unknown. Another basic amino acid, L-lysine, was also shown to cause pancreatic acinar cell injury. The aim of the study was to get insight into the mechanisms through which L-lysine damages the rat exocrine pancreas, in particular to characterize the kinetics of L-lysine-induced mitochondrial injury, as well as the pathologic responses (including alteration of antioxidant systems) characteristic of acute pancreatitis.
  
  
  RESULTS
  We showed that intraperitoneal administration of 2 g/kg L-lysine induced severe acute necrotizing pancreatitis. L-lysine administration caused early pancreatic mitochondrial damage that preceded the activation of trypsinogen and the proinflammatory transcription factor nuclear factor-κB (NF-κB), which are commonly thought to play an important role in the development of acute pancreatitis. Our data demonstrate that L-lysine impairs adenosine triphosphate synthase activity of isolated pancreatic, but not liver, mitochondria.
  
  
  CONCLUSIONS
  Taken together, early mitochondrial injury caused by large doses of L-lysine may lead to the development of acute pancreatitis independently of pancreatic trypsinogen and NF-κB activation.
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Biczó
authors.forename: Péter
authors.initials: P
authors.lastname: Hegyi
authors.forename: Sándor
authors.initials: S
authors.lastname: Dósa
authors.forename: Natalia
authors.initials: N
authors.lastname: Shalbuyeva
authors.forename: Sándor
authors.initials: S
authors.lastname: Berczi
authors.forename: Riitta
authors.initials: R
authors.lastname: Sinervirta
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Hracskó
authors.forename: Andrea
authors.initials: A
authors.lastname: Siska
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kukor
authors.forename: Katalin
authors.initials: K
authors.lastname: Jármay
authors.forename: Viktória
authors.initials: V
authors.lastname: Venglovecz
authors.forename: Ilona S
authors.initials: IS
authors.lastname: Varga
authors.forename: Béla
authors.initials: B
authors.lastname: Iványi
authors.forename: Leena
authors.initials: L
authors.lastname: Alhonen
authors.forename: Tibor
authors.initials: T
authors.lastname: Wittmann
authors.forename: Anna
authors.initials: A
authors.lastname: Gukovskaya
authors.forename: Tamás
authors.initials: T
authors.lastname: Takács
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Rakonczay
mesh_terms: D000208:Acute Disease; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008239:Lysine / Q000633:toxicity*; D008854:Microscopy, Electron; D008928:Mitochondria / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D010179:Pancreas / Q000648:ultrastructure; D010195:Pancreatitis / Q000139:chemically induced / Q000473:pathology*; D051381:Rats
chemical_list: D016328:NF-kappa B; D008239:Lysine