Improved survival in mice with diet-induced pancreatitis treated with new potent protease inhibitor, E-3123 and a broad spectrum antibiotic, cefmetazole.
This study was designed to evaluate the infectious factor in the pathogenesis of acute pancreatitis and the effects of a combination therapy with a new potent protease inhibitor, E-3123, and a broad spectrum antibiotic cefmetazole (CMZ) in mice with CDE diet-induced severe acute pancreatitis. Combination therapy with E-3123 and CMZ showed significant protective effects against the high mortality rate, increased serum amylase and ascitic fluid amylase levels, pancreatic amylase and lysosomal enzyme content, plasma endotoxin levels, redistribution of lysosomal enzyme from the lysosomal to the zymogen fraction, lysosomal and mitochondrial fragility, and also improved the histological findings when compared with the E-3123 alone. These results suggest that infections factors play an important role in the development of severe acute pancreatitis and that protease inhibitors in combination with antibiotics may be clinically beneficial.
Hirano
T
T
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Manabe
T
T
Ohshio
G
G
Nio
Y
Y
D000208:Acute Disease; D000818:Animals; D015311:Cefmetazole / Q000008:administration & dosage*; D016009:Chi-Square Distribution; D002794:Choline / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005001:Ethionine / Q000008:administration & dosage; D005260:Female; D005526:Food, Formulated / Q000009:adverse effects*; D006146:Guanidines / Q000008:administration & dosage*; D051379:Mice; D008815:Mice, Inbred Strains; D010195:Pancreatitis / Q000188:drug therapy* / Q000401:mortality; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage*; D015996:Survival Rate
D006146:Guanidines; D015842:Serine Proteinase Inhibitors; C057059:4-(2-succinimidoethylthio)phenyl 4-guanidinobenzoate; D015311:Cefmetazole; D002794:Choline; D005001:Ethionine