Protective effects of combined therapy with a protease inhibitor, ONO 3307, and a xanthine oxidase inhibitor, allopurinol on temporary ischaemic model of pancreatitis in rats

Abstract

The protective effect of a new potent protease inhibitor, ONO 3307, in combination with a xanthine oxidase inhibitor, allopurinol, was tested in pancreatico-biliary duct obstruction (PBDO) with temporary pancreatic ischemia in rats. After PBDO with ischemia, we observed hyperamylasemia, pancreatic edema, congestion of amylase and lysosomal enzyme cathepsin B as well as impaired output of amylase and cathepsin B into the pancreatic juice and a redistribution of lysosomal enzyme from the lysosomal fraction to the zymogen fraction. The administration of ONO 3307 plus allopurinol almost completely prevented the pancreatic injuries induced by PBDO with ischemia. These results indicate the important roles of temporary pancreatic ischemia in the pathogenesis of pancreatic damage and the usefulness of combination therapy with a new potent protease inhibitor and xanthine oxidase inhibitor in the protection against clinical acute pancreatitis.