The crucial role of early mitochondrial injury in l-lysine-induced acute pancreatitis

György Biczó, Péter Hegyi, Sándor Dósa, Natalia Shalbuyeva, Sándor Berczi, Riitta Sinervirta, Zsuzsanna Hracskó, Andrea Siska, Zoltán Kukor, Katalin Jármay, Viktória Venglovecz, Ilona S. Varga, Béla Iványi, Leena Alhonen, Tibor Wittmann, Anna Gukovskaya, Tamás Takács, Zoltán Rakonczay

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Aims: 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 2g/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. Innovation and Conclusion: 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.

Original languageEnglish
Pages (from-to)2669-2681
Number of pages13
JournalAntioxidants and Redox Signaling
Volume15
Issue number10
DOIs
Publication statusPublished - Nov 15 2011

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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