BACKGROUND: Although several pathophysiological sequences, such as protease activation, free radical generation, and inflammatory mediator release, have been described in acute pancreatitis, the precise mechanism by which acute pancreatitis is initiated is unkown. Cellular calcium, a key function and also a crucial pathological intracellular messenger in cell injury, appears to be involved in the initiation and development of acute pancreatitis. The aim of this study is to evaluate the role of cellular calcium and therapeutic effect of administering the Ca++ channel blocker nicadipine as an antioxidant. METHOD:Nicardipine, known to be a calcium channel blocker and a most potent antioxidant, was wed as a pretreatment 1 hour before induction of pancreatitis by intraductal infusion of 3% sodium taurocholate or as a post-treatment 1 hour after induction of aucte pancreatitis by retrograde infusion of sodium taurocholate. The net weight of the pancrease, the amounts of s-amylse, GSH and MDA in the pancreatic tissue, and the histologic damage were examined 12 hours after the induction of pancreatitis. RESULTS: Nicardipine administration ameliorated pancreatic edema and reduced the amount of s-amylase compare to untreated necrotizing pancreatitis group. Also, pre- or post-treatment with nicardipine had beneficial protective effect with respect to free radical-induced injury; in particular, pre-treatment with nicardipine was much better. With respect to the histologic findings, pancreatic necrosis, hemorrhage, and neutrophil infiltration were prominent in the necrotizing group, however, in the group treated with nicardipine, the necrosis and hemorrhage were ameliorated remarkably. CONCLUSION:The free oxygen radicals and the intracellular calcium influx were major elements in the pathogenesis of acute pancreatitis, and nicardipine ameliorated pancreatic necrosis and hemorrage and exerted an antioxidant effect. The administration of nicardipine should be considered in the early stage of pancreatitis or in case of risk of pancreatitis.
Antioxidants ; Calcium Channels* ; Calcium* ; Edema ; Hemorrhage ; Necrosis ; Neutrophil Infiltration ; Nicardipine* ; Pancreas ; Pancreatitis* ; Pancrelipase ; Reactive Oxygen Species ; Taurocholic Acid

Oxidative radicals are regarded as a major factor in the pathogenesis of both acute and chronic pancreatitis. Because oxygen radicals react most readily with polyunsaturated fatty acids, resulting in peroxidation of lipids, several studies have been performed to determine the development of lipid peroxidation in pancreatitis. The purpose of this study was to evaluate the effects of free radicals and decision of the experimental model in acute necrotizing pancreatitis. Acute necrotizing pancreatitis was induced in 18 rats by retrograde injection into the bilopancreatic duct of 2%, 3%, and 5% sodium taurocholate. After a 12-hour observation time, the pancreas / the body weight, the serum amylase and the malondialdehyde content in tissue, as well as the reduced glutathione were measured in resected tissue samples. In addition, to determine the pathologic damage grade, tissue samples were examined by light microscopy. According to the amount of sodium taurocholate injected, the serum amylase and tissue malondialdehyde concentration were significantly increased. The reduced glutathione was significantly decreased, suggesting glutathione depletion due to oxidative stress. During the 12 hours after injection the pancreatic lesions were immediate and were characterized by interstitial edema, atrophy and extensive necrotic changes of the acinar cells, and hemorrhage. The pathologic damage grade increased according to the amount of sodium taurocholate injected. This study created an experimental model for studying the pathogenesis of acute necrotizing pancreatitis by using bile acid. In acute necrotizing pancreatitis, the increased levels of lipid peroxidation products in tissues and the change in glutathione metabolism suggest ongoing peroxidation of lipids due to an enhanced generation of oxygen radicals. Therefore, antioxidant treatment can reduce tissue damage, biochemical alterations, and extrapancreatic complications, thus improving the final outcome.
Acinar Cells ; Amylases ; Animals ; Atrophy ; Bile ; Body Weight ; Edema ; Fatty Acids, Unsaturated ; Free Radicals ; Glutathione ; Hemorrhage ; Lipid Peroxidation ; Malondialdehyde ; Metabolism ; Microscopy ; Models, Theoretical ; Oxidative Stress* ; Pancreas ; Pancreatitis ; Pancreatitis, Acute Necrotizing* ; Pancreatitis, Chronic ; Rats* ; Reactive Oxygen Species ; Sodium* ; Taurocholic Acid