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DOI: 10.1055/s-0030-1254744
Characterization of pancreatic and extrapancreatic polyamine homeostasis in l-ornithine-induced acute pancreatitis in rats
Introduction: L-ornithine is a precursor of polyamine synthesis that is essential for cell survival. However, intraperitoneal (i.p.) administration of L-ornithine results in severe acute necrotizing pancreatitis in rats.
Aims: To investigate the changes in pancreatic and extrapancreatic (lung and liver) polyamine homeostasis after injection of a large dose of L-ornithine and to test the effects of the stable polyamine analogue methylspermidine (MeSpd) on L-ornithine-induced acute necrotizing pancreatitis.
Methods: Male Wistar rats were injected intraperitoneally (i.p.) with 3g/kg L-ornithine and/or physiological saline and were untreated, pretreated or treated with 50mg/kg MeSpd i.p. Rats were sacrificed after 0–168h for determinations of pancreatic and extrapancreatic concentrations of spermidine, spermine, and putrescine, and activities of ornithine decarboxylase and spermidine/spermine N1-acetyltransferase (SSAT). Besides measuring polyamine levels and SSAT activity, the severity of pancreatitis was assessed by measuring standard laboratory and histological parameters.
Results: Administration of 3g/kg L-ornithine paradoxically induced marked pancreatic spermidine catabolism, possibly via activation of SSAT, after (>6h) appearance of first histological signs of acute pancreatitis. In contrast, polyamine levels were generally increased in the lung and liver with the exception of lung spermidine levels which decreased. Pretreatment or treatment with MeSpd did not influence the levels of natural polyamines and SSAT activity and did not alter the severity of L-ornithine-induced acute pancreatitis.
Conclusions: L-ornithine-induced acute pancreatitis was associated with activation of pancreatic polyamine catabolism. However, in this model, polyamine catabolism is unlikley to play a role in the initiation of pancreatic injury. Administration of MeSpd did not affect disease severity. Supported by OTKA, NKTH, MTA and Academy of Finland.