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 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. 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.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Biczó G,Hegyi P,Dósa S,Shalbuyeva N,Berczi S,Sinervirta R,Hracskó Z,Siska A,Kukor Z,Jármay K,Venglovecz V,Varga IS,Iványi B,Alhonen L,Wittmann T,Gukovskaya A,Takács T,Rakonczay Z Jrdoi
10.1089/ars.2011.4065subject
Has Abstractpub_date
2011-11-15 00:00:00pages
2669-81issue
10eissn
1523-0864issn
1557-7716journal_volume
15pub_type
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