Oxidative stress in distant organs and the effects of allopurinol during experimental acute pancreatitis

Background. The present study was aimed at an assessment of the role of oxy gen-derived free radicals in the development of local and systemic manifest ations 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 o f glycine. In a third group, 200 mg/kg of allopurinol was administered subc utaneously 30 min before the first Arg injection. Rats were killed at 6, 12 , 24, or 48 h following Arg administration. acute pancreatitis was confirme d 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 activ ities were reduced in the liver after the onset of pancreatitis. Histologic examination revealed acinar cell necrosis in the pancreas, but only mild a lterations in the liver and kidney. Allopurinol pretreatment prevented the generation of reactive oxygen metabolites in the pancreas and reduced their formation in the kidney. Conclusion. Oxygen-derived free radicals are generated in the pancreas, liv er, and kidney at an early stage of Arg-induced acute pancreatitis. The liv er and the kidney, but not the pancreas, are able to defend against oxidati ve stress. The prophylactic application of allopurinol significantly restra ins the generation of free radicals in pancreas and kidney.