A new synthetic protease inhibitor, E-3123, prevents lysosomal and mitochondrial fragility in rat caerulein-induced pancreatitis.
The study investigated the protective effect of a new synthetic protease inhibitor, E-3123, a 4-guanidinobenzoate methanesulphonate, on the exocrine pancreas in caerulein-induced pancreatitis of rats both in vivo and in vitro. Hyperamylasaemia, pancreatic oedema and congestion of amylase, as well as cathepsin B leakage from lysosomes and malate dehydrogenase leakage from mitochondria, were prevented by infusion of 5 mg/kg.h E-3123 particularly when infused for 2 h before and during 5 micrograms/kg.h caerulein infusion for 3.5 h. The results indicate that E-3123 plays its protective roles against pancreatitis in the subcellular compartments such as lysosomes and mitochondria, and that such a low molecular weight protease inhibitor as E-3123 may be clinically useful in the treatment of acute pancreatitis.
Hirano
T
T
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Manabe
T
T
D000208:Acute Disease; D000681:Amylases / Q000097:blood / Q000378:metabolism; D000818:Animals; D001834:Body Water / Q000378:metabolism; D002108:Ceruletide; D006146:Guanidines / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects / Q000648:ultrastructure*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure*; D010179:Pancreas / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D010195:Pancreatitis / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
D006146:Guanidines; D015842:Serine Proteinase Inhibitors; C057059:4-(2-succinimidoethylthio)phenyl 4-guanidinobenzoate; D002108:Ceruletide; D000681:Amylases