title: Hyperlipidemia induced by a cholesterol-rich diet aggravates necrotizing pancreatitis in rats.
abstract: The aim of the present study was to investigate whether hyperlipidemia can cause acute pancreatitis or alter its severity. Male Wistar rats were fed a 3% cholesterol-enriched diet or a normal diet for 16 weeks. Edematous and necrotizing pancreatitis was induced with 3x75 mug/kg body weight of cholecystokinin s.c. and 2x2 g/kg body weight of L-arginine i.p., respectively, in separate groups of normal and hyperlipidemic rats. The severity of the pancreatitis was assessed. We studied the influence of hyperlipidemia on the formation 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) activation in the pancreas during acute edematous and necrotizing pancreatitis. Hyperlipidemia did not worsen edematous, but aggravated necrotizing pancreatitis. The cholesterol-enriched diet significantly reduced the catalase and Mn-superoxide dismutase (SOD) and constitutive NOS (cNOS) activities and increased the inducible NOS (iNOS) in the pancreas relative to those in the rats on the normal diet. The pancreatic nitrotyrosine level, as a marker of ONOO(-), and the NF-kappaB DNA-binding activity in the pancreas, were significantly elevated in the cholesterol-fed rats. The pancreatic HSP72 expression during necrotizing pancreatitis was not influenced by the hyperlipidemia. The pancreatic Mn-SOD, Cu, Zn-SOD, glutathione peroxidase, total glutathione and cNOS activities were significantly reduced, while the catalase, iNOS and NF-kappaB DNA-binding activities were significantly increased in the animals with necrotizing pancreatitis on the cholesterol diet as compared with those with pancreatitis and receiving the normal diet. Hyperlipidemia induced with this cholesterol-enriched diet leads to decreases in endogenous scavenger and cNOS activities, results in iNOS and NF-kappaB activation and stimulates ONOO(-) generation in the pancreas, which may be responsible for the aggravation of acute necrotizing pancreatitis.
authors.affiliation: First Department of Medicine, University of Szeged, Hungary. czal@in1st.szote.u-szeged.hu
authors.forename: László
authors.initials: L
authors.lastname: Czakó
authors.forename: Annamária
authors.initials: A
authors.lastname: Szabolcs
authors.forename: Agota
authors.initials: A
authors.lastname: Vajda
authors.forename: Sándor
authors.initials: S
authors.lastname: Csáti
authors.forename: Viktória
authors.initials: V
authors.lastname: Venglovecz
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Rakonczay
authors.forename: Péter
authors.initials: P
authors.lastname: Hegyi
authors.forename: László
authors.initials: L
authors.lastname: Tiszlavicz
authors.forename: Tamás
authors.initials: T
authors.lastname: Csont
authors.forename: Anikó
authors.initials: A
authors.lastname: Pósa
authors.forename: Anikó
authors.initials: A
authors.lastname: Berkó
authors.forename: Csaba
authors.initials: C
authors.lastname: Varga
authors.forename: Szollosiné
authors.initials: S
authors.lastname: Varga Ilona
authors.forename: Imre
authors.initials: I
authors.lastname: Boros
authors.forename: János
authors.initials: J
authors.lastname: Lonovics
mesh_terms: D000818:Animals; D001120:Arginine; D002374:Catalase / Q000378:metabolism; D002766:Cholecystokinin; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000009:adverse effects*; D016166:Free Radical Scavengers / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D006949:Hyperlipidemias / Q000150:complications / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D010179:Pancreas / Q000378:metabolism; D019283:Pancreatitis, Acute Necrotizing / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D002791:Cholesterol, Dietary; D016166:Free Radical Scavengers; D050884:HSP72 Heat-Shock Proteins; D016328:NF-kappa B; D030421:Peroxynitrous Acid; D002766:Cholecystokinin; D001120:Arginine; D002374:Catalase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase