In vivo Assessment for the Antioxidant Activity of the Calcium Channel Blocker Nicardipine in 3% Sodium-Taurocholate-induced Acute Pancreatitis

ABSTRACT

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.