A new synthetic protease inhibitor, E-3123, reduces organelle fragility of acinar cells in rat caerulein pancreatitis
Hirano, T.; Manabe, T.; Imanishi, K.; Yotsumoto, F.; Kyogoku, T.; Tobe, T.
Nihon Geka Hokan. Archiv für Japanische Chirurgie 60(6): 406-414
1991
ISSN/ISBN: 0003-9152 PMID: 1820013 Document Number: 375642
The present study investigated the protective effect of a new potent synthetic protease inhibitor, E-3123 (4-guanidinobenzoate methanesulfonate) on the exocrine pancreas in the caerulein induced experimental pancreatitis both in-vivo and in-vitro at 3 different doses (1, 2, and 5 mg/kg.hr). This protease inhibitor prevented hyperamylasemia, pancreatic edema, congestion of amylase, and both amylase and lactic dehydrogenase (LDH) discharge from dispersed acini, as well as cathepsin B leakage from lysosomes and malate dehydrogenase (MDH) leakage from mitochondria in a dose-dependent manner, particularly in doses of 2 and 5 mg/kg.hr. Furthermore, the combined prophylactic and therapeutic use of this agent seems to be very effective in preventing caerulein induced pancreatitis. These results indicate that E-3123 plays its protective roles against pancreatitis in the subcellular compartment: lysosomes, mitochondria, cellular or organella membranes. It is hoped that such a low molecular weight protease inhibitor as E-3123 will be clinically useful in the treatment of acute pancreatitis.