Depletion of pancreatic intracellular
polyamine pools has been observed in
acute pancreatitis both in the animal models and in humans. In this study, the wild-type mice,
polyamine catabolic
enzyme spermidine/spermine N(1)-acetyltransferase overexpressing (SSAT mice) and SSAT-deficient mice were used to characterize the new
zinc-induced
acute pancreatitis mouse model and study the role of
polyamines and
polyamine catabolism in this model. Intraperitoneal
zinc injection induced
acute necrotizing pancreatitis in wild-type mice as well as in SSAT-overexpressing and SSAT-deficient mice. Serum α-
amylase activity was significantly increased in all
zinc-treated mice compared with the untreated controls. However, the α-
amylase activities in SSAT mice were constantly lower than those in the other groups. Histopathological examination of pancreatic tissue revealed
edema, acinar cell
necrosis and necrotizing
inflammation, typical for
acute pancreatitis. Compared with the other
zinc-treated mice less damage according to the histopathological analysis was observed in the pancreatic tissue of SSAT mice. Levels of intracellular
spermidine, and occasionally
spermine, were significantly decreased in pancreases of all
zinc-treated animals and SSAT
enzyme activity was enhanced both in wild-type and SSAT mice. Interestingly, a
spermine analog, N(1), N(11)-diethylnorspermine (
DENSpm), enhanced the proliferation of pancreatic cells and reduced the severity of
zinc-induced
pancreatitis in wild-type mice. The results show that in mice a single intraperitoneal
zinc injection causes
acute necrotizing pancreatitis accompanied by decrease of intracellular
polyamine pools. The study supports the important role of
polyamines for the integrity and function of the pancreas. In addition, the study suggests that whole body overexpression of SSAT obtained in SSAT mice reduces inflammatory pancreatic cell injury.