AIM: To assess the role of oxygen-derived free radicals and cytokines in the pathogenesis of taurocholic acid-induced acute pancreatitis, and to evaluate the preventive effects of octreotide towards the development of...AIM: To assess the role of oxygen-derived free radicals and cytokines in the pathogenesis of taurocholic acid-induced acute pancreatitis, and to evaluate the preventive effects of octreotide towards the development of acute pancreatitis. METHODS: Acute pancreatitis was induced in male New Zealand white rabbits by retrograde injection of 0.8 mL/kg·b·m, of 50 g/L sodium taurocholate(NaTC) in the pancreatic duct. Sham-operated animals served as control. Octreotide 1 mglkg·b.m.was administered subcutaneously before the induction of pancreatitis. Blood was taken from the jugular vein before and at 1, 3, 6, 12 and 24 h after pancreatitis induction.Serum activities of amylase, IL-6 and TNF-α and levels of malonyl dialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), catalase and superoxide dismutase (Mn-,Cu-,and Zn-SOD) in pancreatic tissue were measured.RESULTS: Serum TNF-α and IL-6 levels increased significantly 3 h after the onset of pancreatitis, and then returned to control level. The tissue concentration of MDA was significantly elevated at 24 h, while the GSH level and GP-x, catalase, Mn-SOD, Cu-, Zn-SOD activities were all significantly decreased in animals with pancreatitis as compared to the control. Octreotide pretreatment significantly reversed the changes in cytokines and reactive oxygen metabolites. Octreotide treatment did not alter the serum amylase activity and did not have any beneficial effects on the development of histopathological changes.CONCLUSION: Oxygen-derived free radicals and proinflammatory cytokines are generated at an early stage of NaTc-induced acute pancreatitis in rabbits. Prophylac ticoctreotide treatment can prevent release of cytokines and generation of reactive oxygen metabolites, but does not have any beneficial effects on the development of necrotizing pancreatitis.展开更多
Despite medical treatment, the lethality of severe acute pancreatitis is still high (20-30%). Therefore, it is very important to find good animal models to characterise the events of this severe disease. In 1984, Mizu...Despite medical treatment, the lethality of severe acute pancreatitis is still high (20-30%). Therefore, it is very important to find good animal models to characterise the events of this severe disease. In 1984, Mizunuma et. al. developed a new type of experimental necrotizing pancreatitis by intraperitoneal administration of a high dose of L-arginine in rats. This non-invasive model is highly reproducible and produces selective, dose-dependent acinar cell necrosis.Not only is this a good model to study the pathomechanisne of acute necrotizing pancreatitis, but it is also excellent to observe and influence the time course changes of the disease. By writing this review we iluminate some new aspects of cell physiology and pathology of acute necrotizing pancreatitis. Unfortunately, the reviews about acute experimental pancreatitis usually did not discuss this model.Therefore, the aim of this manuscript was to summarise the observations and address some challenges for the future in L-arginine-induced pancreatitis.展开更多
基金Supported by the grant from the Hungarian Scieutigic Research Found (OTKA No.D34004) the Hungarian Academy of Sciences (B0 5/2003) and ETT SK503
文摘AIM: To assess the role of oxygen-derived free radicals and cytokines in the pathogenesis of taurocholic acid-induced acute pancreatitis, and to evaluate the preventive effects of octreotide towards the development of acute pancreatitis. METHODS: Acute pancreatitis was induced in male New Zealand white rabbits by retrograde injection of 0.8 mL/kg·b·m, of 50 g/L sodium taurocholate(NaTC) in the pancreatic duct. Sham-operated animals served as control. Octreotide 1 mglkg·b.m.was administered subcutaneously before the induction of pancreatitis. Blood was taken from the jugular vein before and at 1, 3, 6, 12 and 24 h after pancreatitis induction.Serum activities of amylase, IL-6 and TNF-α and levels of malonyl dialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), catalase and superoxide dismutase (Mn-,Cu-,and Zn-SOD) in pancreatic tissue were measured.RESULTS: Serum TNF-α and IL-6 levels increased significantly 3 h after the onset of pancreatitis, and then returned to control level. The tissue concentration of MDA was significantly elevated at 24 h, while the GSH level and GP-x, catalase, Mn-SOD, Cu-, Zn-SOD activities were all significantly decreased in animals with pancreatitis as compared to the control. Octreotide pretreatment significantly reversed the changes in cytokines and reactive oxygen metabolites. Octreotide treatment did not alter the serum amylase activity and did not have any beneficial effects on the development of histopathological changes.CONCLUSION: Oxygen-derived free radicals and proinflammatory cytokines are generated at an early stage of NaTc-induced acute pancreatitis in rabbits. Prophylac ticoctreotide treatment can prevent release of cytokines and generation of reactive oxygen metabolites, but does not have any beneficial effects on the development of necrotizing pancreatitis.
基金Supported by The Wellcome Trust,Grant No.022618,and by the Hungarian Scientific Research Fund,No.D42188,T43066 and T042589
文摘Despite medical treatment, the lethality of severe acute pancreatitis is still high (20-30%). Therefore, it is very important to find good animal models to characterise the events of this severe disease. In 1984, Mizunuma et. al. developed a new type of experimental necrotizing pancreatitis by intraperitoneal administration of a high dose of L-arginine in rats. This non-invasive model is highly reproducible and produces selective, dose-dependent acinar cell necrosis.Not only is this a good model to study the pathomechanisne of acute necrotizing pancreatitis, but it is also excellent to observe and influence the time course changes of the disease. By writing this review we iluminate some new aspects of cell physiology and pathology of acute necrotizing pancreatitis. Unfortunately, the reviews about acute experimental pancreatitis usually did not discuss this model.Therefore, the aim of this manuscript was to summarise the observations and address some challenges for the future in L-arginine-induced pancreatitis.