title: Oxidative stress in distant organs and the effects of allopurinol during experimental acute pancreatitis.
abstract: BACKGROUND
  The present study was aimed at an assessment of the role of oxygen-derived free radicals in the development of local and systemic manifestations of L-arginine (Arg)-induced acute pancreatitis and at an evaluation of the protective effect of the xanthine oxidase inhibitor allopurinol.
  
  
  METHODS
  Acute pancreatitis was induced in male Wistar rats by injecting 2 x 250 mg/100 g body weight of Arg intraperitoneally at an interval of 1 h, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. In a third group, 200 mg/kg of allopurinol was administered subcutaneously 30 min before the first Arg injection. Rats were killed at 6, 12, 24, or 48 h following Arg administration. Acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features were observed microscopically. Tissue concentrations of malonyl dialdehyde (MDA), superoxide dismutase (Mn- and Cu,Zn-SOD), glutathione peroxidase (GPx), and catalase were measured in the pancreas, liver, and kidney.
  
  
  RESULTS
  The tissue concentration of MDA was significantly elevated in each organ. The activities of Mn-SOD, Cu,Zn-SOD, GPx, and catalase were quickly depleted in the pancreas and kidney, whereas only the Mn-SOD and GPx activities were reduced in the liver after the onset of pancreatitis. Histologic examination revealed acinar cell necrosis in the pancreas, but only mild alterations in the liver and kidney. Allopurinol pretreatment prevented the generation of reactive oxygen metabolites in the pancreas and reduced their formation in the kidney.
  
  
  CONCLUSIONS
  Oxygen-derived free radicals are generated in the pancreas, liver, and kidney at an early stage of Arg-induced acute pancreatitis. The liver and the kidney, but not the pancreas, are able to defend against oxidative stress. The prophylactic application of allopurinol significantly restrains the generation of free radicals in pancreas and kidney.
authors.affiliation: First Department of Medicine, Albert Szent-Gyorgyi Medical University, Attila József University, Szeged, Hungary. czal@in1st.szote.u-szeged.hu
authors.forename: L
authors.initials: L
authors.lastname: Czakó
authors.forename: T
authors.initials: T
authors.lastname: Takács
authors.forename: I S
authors.initials: IS
authors.lastname: Varga
authors.forename: L
authors.initials: L
authors.lastname: Tiszlavicz
authors.forename: D Q
authors.initials: DQ
authors.lastname: Hai
authors.forename: P
authors.initials: P
authors.lastname: Hegyi
authors.forename: B
authors.initials: B
authors.lastname: Matkovics
authors.forename: J
authors.initials: J
authors.lastname: Lonovics
mesh_terms: D000208:Acute Disease; D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D018384:Oxidative Stress; D010195:Pancreatitis / Q000209:etiology* / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000502:physiology
chemical_list: D008315:Malondialdehyde; D000493:Allopurinol; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase