RESUMO
The purpose of this study was to verify whether injection of tert-butyl hydroperoxide (Bu(t)OOH, a well-known prooxidant agent) into the bile-pancreatic duct can induce acute pancreatitis. A rapid blockade of the secretion was observed in the majority of the animals after 3 hours of observation. After 6 hours, the secretion reached a very low level, significantly different compared with controls. In groups of rats injected with Bu(t)OOH, pancreatic weight gain was observed compared with the rats injected with physiologic saline. Histology of pancreata removed 3 hours after injection of Bu(t)OOH showed acinar cell vacuolization, interstitial edema, focal necrosis of pancreatic acini, fat-tissue necrosis, and leukocyte infiltration of the organ. These changes were considerably greater after the 6-hour observation period. Electron-microscopic inspection revealed profound morphologic changes 3 hours after Bu(t)OOH injection. The control rats receiving physiologic saline alone had well-preserved pancreatic tissue structure. In conclusion, injection of the prooxidant agent, tert-butyl hydroperoxide, into common bile-pancreatic duct induces acute necrotizing pancreatitis, which indicates the crucial role of free radical reactions in pathogenesis of this disease.
Assuntos
Modelos Animais de Doenças , Pancreatite/induzido quimicamente , terc-Butil Hidroperóxido/toxicidade , Animais , Masculino , Microscopia Eletrônica , Pâncreas/patologia , Pâncreas/ultraestrutura , Pancreatite/patologia , Ratos , Ratos WistarRESUMO
CONCLUSION: Subcellular organelles and membranes were the structures most protected by allopurinol, indirectly demonstrating their role of main and early target of oxygen-derived free radicals in the pathogenesis of acute pancreatitis. BACKGROUND: The present work evaluates the ultrastructural changes during cerulein-induced acute pancreatitis in rat, with and without treatment with allopurinol. METHODS AND RESULTS: Supramaximal doses of cerulein, injected intraperitoneally (50 microg/kg) twice, at 1-h interval, caused severe subcellular alterations, including zymogen distribution, pathological vacuoles, and damage to organelles and membranes. Cotreatment (40 mg/kg ip twice with 1-h interval; n = 10 rats) and, most of all, pretreatment (40 mg/kg ip allopurinol, 1 h; 20 mg/kg ip allopurinol + 50 microg/kg ip cerulein, 30 min; 40 mng/kg ip allopurinol, 30 min; 50 microg/kg ip cerulein; n = 10 rats) with allopurinol showed significant morphological improvement.