A new synthetic protease inhibitor, E-3123, reduces organelle fragility of acinar cells in rat caerulein pancreatitis.

Abstract

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.

• Authors: T Hirano, T Manabe, K Imanishi, F Yotsumoto, T Kyogoku, T Tobe
• Journal: Nihon geka hokan. Archiv fur japanische Chirurgie (Nihon Geka Hokan) Vol. 60 Issue 6 Pg. 406-14 (Nov 01 1991) ISSN: 0003-9152 [Print] Japan
• PMID: 1820013 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Guanidines
• Serine Proteinase Inhibitors
• 4-(2-succinimidoethylthio)phenyl 4-guanidinobenzoate
• Ceruletide

Topics

• Acute Disease
• Animals
• Ceruletide
• Guanidines (pharmacology)
• Male
• Organelles (drug effects, metabolism)
• Osmotic Fragility (drug effects)
• Pancreas (drug effects, metabolism)
• Pancreatitis (chemically induced, metabolism)
• Rats
• Rats, Inbred Strains
• Serine Proteinase Inhibitors (pharmacology)