The aim of the present study was to inves
tigate whether hyperlipidemia can cause acute pancrea
titis or alter its severity. Male Wistar rats were fed a 3% cholesterol-enriched diet or a normal diet for 16 weeks. Edematous and necro
tizing pancrea
titis was induced with 3x75 mug/kg body weight of cholecystokinin s.c. and 2x2 g/kg body weight of L-arginine i.p., respec
tively, in separate groups of normal and hyperlipidemic rats. The severity of the pancrea
titis was assessed. We studied the influence of hyperlipidemia on the forma
tion of oxygen-derived free radicals, endogenous scavengers, nitric oxide synthases (NOS), peroxynitrite (ONOO(-)), heat shock protein 72 (HSP72) and nuclear factor-kappa B (NF-kappaB) ac
tiva
tion in the pancreas during acute edematous and necro
tizing pancrea
titis. Hyperlipidemia did not worsen edematous, but aggravated necro
tizing pancrea
titis. The cholesterol-enriched diet significantly reduced the catalase and Mn-superoxide dismutase (SOD) and cons
titu
tive NOS (cNOS) ac
tivi
ties and increased the inducible NOS (iNOS) in the pancreas rela
tive to those in the rats on the normal diet. The pancrea
tic nitrotyrosine level, as a marker of ONOO(-), and the NF-kappaB DNA-binding ac
tivity in the pancreas, were significantly elevated in the cholesterol-fed rats. The pancrea
tic HSP72 expression during necro
tizing pancrea
titis was not influenced by the hyperlipidemia. The pancrea
tic Mn-SOD, Cu, Zn-SOD, glutathione peroxidase, total glutathione and cNOS ac
tivi
ties were significantly reduced, while the catalase, iNOS and NF-kappaB DNA-binding ac
tivi
ties were significantly increased in the animals with necro
tizing pancrea
titis on the cholesterol diet as compared with those with pancrea
titis and receiving the normal diet. Hyperlipidemia induced with this cholesterol-enriched diet leads to decreases in endogenous scavenger and cNOS ac
tivi
ties, results in iNOS and NF-kappaB ac
tiva
tion and s
timulates ONOO(-) genera
tion in the pancreas, which may be responsible for the aggrava
tion of acute necro
tizing pancrea
titis.
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