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.
