Objectives: l-Ornithine is a precursor of polyamine synthesis that is essential for cell survival. In contrast, intraperitoneal (IP) administration of a large dose of l-ornithine results in death of pancreatic acinar cells in rats. We investigated changes in pancreatic and extrapancreatic polyamine homeostasis after injection of l-ornithine and tested the effects of the stable polyamine analogue methylspermidine (MeSpd) on l-ornithine-induced pancreatitis.
Methods: Male Wistar rats were injected IP with 3 g/kg l-ornithine and were untreated, pretreated, or treated with 50 mg/kg MeSpd IP. Rats were killed after 0 to 168 hours for determinations of polyamines and activities of ornithine decarboxylase and spermidine/spermine N(1)-acetyltransferase (SSAT). Pancreatitis severity was assessed by measuring standard laboratory and histological parameters.
Results: Injection of l-ornithine paradoxically induced pancreatic spermidine catabolism, possibly via activation of SSAT, after (>6 hours) appearance of the first histological signs of acute pancreatitis. Polyamine levels generally increased in the lung and liver with the exception of lung spermidine levels, which decreased. Methylspermidine did not influence polyamine levels and SSAT activity and did not ameliorate the severity of l-ornithine-induced pancreatitis.
Conclusions: l-Ornithine-induced pancreatitis was associated with activation of pancreatic polyamine catabolism. However, administration of a metabolically stable polyamine analogue did not affect disease severity.