Effect of 5-fluorouracil (5-FU) on the isolated perfused rat pancreas

This study was designed to evaluate the effect of anticancer agent 5-fluorouracil (5-FU)) on the exocrine pancreas by using isolated perfused rat pancreas at three different doses (2.5, 5.0 and 10 microg/ml). 5-FU at doses of 5 and 10 microg/ml for 1 h caused significant increases in amylase levels in pancreatic effluent and significant decreases in amylase outputs. Moreover, 5-FU caused significant increases in pancreatic trypsin contents in pancreatic tissue. 5-FU also caused significant redistribution of cathepsin B activity from the lysosomal fraction to the zymogen fraction in pancreatic subcellular fractionation study. These changes were almost dose-dependent. These results suggest that the exocrine pancreas might be injured by 5-FU, and that lysosomal enzymes seem to play an important role in the pathogenesis of the pancreatic injuries induced by 5-FU, since cathepsin B can activate trypsinogen.