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.
Hirano
T
T
Department of Surgery, Hirano Clinic, Izumisano, Osaka, Japan.
Hirano
K
K
D000681:Amylases / Q000378:metabolism; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001834:Body Water / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D000681:Amylases; D014357:Trypsin; D002401:Cathepsin B; D005472:Fluorouracil