Document Detail


E-3123, a new synthetic protease inhibitor, protects against deoxycholic acid-induced acute pancreatitis in dogs.
MedLine Citation:
PMID:  1711836     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of intravenous infusion of 4-(2-succinimidoethylthio)phenyl 4-guanidinobenzoate (E-3123), a new synthetic protease inhibitor, on deoxycholic acid-induced acute pancreatitis in a canine pancreas were investigated. The retrograde injection of 1% deoxycholic acid into the pancreatic duct significantly and time-dependently increased venous serum amylase and lipase activities. E-3123 significantly decreased these increased amylase and lipase activities. Two hours after deoxycholic acid injection, the amylase activity was reduced by 23 +/- 3% and 34 +/- 4% after infusion of 0.1 and 1 mg/kg/hr of E-3123, respectively, compared to the corresponding values in the control group, and the lipase activity was reduced by 13 +/- 3% and 29 +/- 3%, respectively. The potency of 1 mg of E-3123 to decrease these enzymes was almost the same as that of 5 mg of gabexate, a novel protease inhibitor. Pancreatic wet weight/body weight also decreased after treatment with E-3123 in dogs injected with deoxycholic acid. Histologic examination revealed that injection with deoxycholic acid caused marked interstitial edema, hemorrhage, vacuolization and inflammation as well as focal acinar cell necrosis, while in the E-3123-treated group, only mild changes in these parameters were seen. These results suggest that E-3123 may be useful in suppressing the progression of acute pancreatitis induced by deoxycholic acid, at least in part, through its protease-inhibiting ability.
Authors:
K Iwatsuki; A Horiuchi; H Yonekura; L M Ren; S Chiba
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Archives internationales de pharmacodynamie et de thérapie     Volume:  308     ISSN:  0003-9780     ISO Abbreviation:  Arch Int Pharmacodyn Ther     Publication Date:    1990 Nov-Dec
Date Detail:
Created Date:  1991-07-26     Completed Date:  1991-07-26     Revised Date:  2012-01-12    
Medline Journal Info:
Nlm Unique ID:  0405353     Medline TA:  Arch Int Pharmacodyn Ther     Country:  BELGIUM    
Other Details:
Languages:  eng     Pagination:  168-77     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Amylases / blood
Animals
Deoxycholic Acid / antagonists & inhibitors*
Dogs
Female
Gabexate
Guanidines / pharmacology*
Lipase / blood
Male
Organ Size / drug effects
Pancreas / pathology
Pancreatitis / chemically induced,  pathology,  prevention & control*
Serine Proteinase Inhibitors / pharmacology*
Chemical
Reg. No./Substance:
0/Guanidines; 0/Serine Proteinase Inhibitors; 114568-26-2/4-(2-succinimidoethylthio)phenyl 4-guanidinobenzoate; 39492-01-8/Gabexate; 83-44-3/Deoxycholic Acid; EC 3.1.1.3/Lipase; EC 3.2.1.-/Amylases

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