Background: The aim of the present study was to investigate whether hyperlipidemia can cause
acute pancreatitis or alter its severity. We studied the influence of cholesterol-enriched
diet-induced hyperlipidemia on the formation of pancreatic nitric oxide synthase (NOS),
oxygen-derived free radicals, endogenous scavengers, heat shock proteins and nuclear
factor-kappaB during acute edematous and necrotizing pancreatitis.
Methods: Male Wistar rats were fed a 3% cholesterol-enriched diet or a normal diet for 16
weeks. Edematous pancreatitis was induced with 3×75µg/kg bw cholecystokinin s.c.,
and necrotizing pancreatitis with 2×200mg/100g bw of L-arginine i.p., in separate
groups of normal and hyperlipidemic rats. The rats were sacrificed 24h following the
induction of pancreatitis, and the severity of the pancreatitis was assessed by measurement
of the plasma amylase and lipase concentrations, and the ratio pancreatic weight/body
weight (pw/bw), and via the histology.
Results: The cholesterol diet increased the plasma cholesterol and triglyceride levels by
40% and 90%, respectively. The pancreatic cNOS activity was significantly reduced,
while the iNOS activity was significantly increased in the hyperlipidemic rats as
compared with the non-hyperlipidemic animals 0.1 pmol/min/mg protein). The±2.8 vs.
1.03±1.8 and 10.8±5.6 vs. 36.1±(12.7 cholesterol diet did not worsen the levels of
serum amylase and lipase, the ratio pw/bw or the histological score in the animals
with edematous pancreatitis. In the animals with necrotizing pancreatitis, the serum
amylase and lipase levels, the ratio pw/bw ratio and the histological score were significantly
increased in the hyperlipidemic animals as compared with the non-hyperlipidemic animals.
Conclusion: Cholesterol-enriched diet-induced hyperlipidemia leads to a decrease in pancreatic
cNOS activity and an increase in iNOS activity, which may contribute to the aggravation
of necrotizing pancreatitis.
