Possible Involvement of Nitric Oxide (NO) as a Free Radical in the Pathogenesis of Pancreatic Ischemia-Reperfusion Injuries in Rats

Abstract

This study was designed to evaluate the role of nitric oxide (NO) as a free radical in the pathogenesis of pancreatic injuries induced by pancreatic ischemia-reperfusion in rats. Pancreatic ischemia-reperfusion was accomplished by reducing the mean arterial blood pressure approximately to 60% of the control values for 45 minutes with blood removal and by restoring normotension by reinfusion of the shed blood. In this model of pancreatic ischemia-reperfusion, serum amylase concentrations, pancreatic water content, and pancreatic trypsin content were significantly increased as compared with the control animals. Pancreatic superoxide dismutase (SOD) content was significantly decreased. However, pancreatic lipid peroxide (LPO) levels were significantly increased. Moreover, pancreatic subcellular redistribution of lysosomal enzyme, cathepsin B, from the lysosomal fraction to the zymogen fraction was also observed. Pretreatment with NO synthase inhibitor, N ω-nitro-L-arginine (NNA) at a dose of 20 mg/kg, significantly inhibited these changes. These results indicate that NO seems to play an important role as a free radical in the pathogenesis of pancreatic injuries induced by pancreatic ischemia-reperfusion and that NO seems to be involved in the intracellular sorting of lysosomal enzymes in the pancreatic acinar cells during pancreatic ischemia-reperfusion.

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