Combined therapy of a cephalosporin, Shiomarin and a new potent protease inhibitor, E3123 in rat taurocholate-induced pancreatitis.

The role of infectious factors in the pathogenesis of acute pancreatitis and the protective effect of combined therapy with a new potent synthetic protease inhibitor, E3123, and a new potent synthetic cephalosporin, Shiomarin (SM) were examined in rat acute pancreatitis. Sodium taurocholate injection into the pancreatico-biliary duct of rats caused severe pancreatitis with a high mortality rate, characterized by hyperamylasemia, high amylase activity in ascitic fluid, and hyperendotoxemia and a high serum level of fibrin degradation products (FDP), redistribution of cathepsin B from the lysosomal fraction to the zymogen fraction. In rats with E3123 infusion almost all parameters were improved, including mortality rate, serum and ascitic fluid amylase levels, plasma endotoxin and serum FDP levels, and distribution of lysosomal enzyme. But combination therapy with E3123 and SM was significantly more protective than E3123 therapy alone. These results indicate that infection plays an important role in the development of severe pancreatitis and that combination therapy with a new synthetic protease inhibitor and a new potent antibiotic may be useful in the treatment of severe pancreatitis.