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

György Biczó, P. Hegyi, Sándor Dósa, Natalia Shalbuyeva, Sándor Berczi, Riitta Sinervirta, Zsuzsanna Hracskó, Andrea Siska, Z. Kukor, K. Jármay, V. Venglovecz, I. Varga, B. Iványi, Leena Alhonen, T. Wittmann, Anna Gukovskaya, T. Takács, Z. Rakonczay

Research output: Contribution to journalArticle

23 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

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Pancreatitis
Lysine
Wounds and Injuries
Trypsinogen
Basic Amino Acids
Complement Factor B
Chemical activation
Acute Necrotizing Pancreatitis
Exocrine Pancreas
Mitochondria
Ornithine
Acinar Cells
Liver Mitochondrion
Liver
Toxicity
Arginine
Rats
Rodentia
Transcription Factors
Antioxidants

ASJC Scopus subject areas

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

Cite this

The crucial role of early mitochondrial injury in l-lysine-induced acute pancreatitis. / Biczó, György; Hegyi, P.; Dósa, Sándor; Shalbuyeva, Natalia; Berczi, Sándor; Sinervirta, Riitta; Hracskó, Zsuzsanna; Siska, Andrea; Kukor, Z.; Jármay, K.; Venglovecz, V.; Varga, I.; Iványi, B.; Alhonen, Leena; Wittmann, T.; Gukovskaya, Anna; Takács, T.; Rakonczay, Z.

In: Antioxidants and Redox Signaling, Vol. 15, No. 10, 15.11.2011, p. 2669-2681.

Research output: Contribution to journalArticle

Biczó, György ; Hegyi, P. ; Dósa, Sándor ; Shalbuyeva, Natalia ; Berczi, Sándor ; Sinervirta, Riitta ; Hracskó, Zsuzsanna ; Siska, Andrea ; Kukor, Z. ; Jármay, K. ; Venglovecz, V. ; Varga, I. ; Iványi, B. ; Alhonen, Leena ; Wittmann, T. ; Gukovskaya, Anna ; Takács, T. ; Rakonczay, Z. / The crucial role of early mitochondrial injury in l-lysine-induced acute pancreatitis. In: Antioxidants and Redox Signaling. 2011 ; Vol. 15, No. 10. pp. 2669-2681.
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