Document Detail

Effects of a novel elastase inhibitor, ONO-5046, on nephrotoxic serum nephritis in rats.
MedLine Citation:
PMID:  9573534     Owner:  NLM     Status:  MEDLINE    
ONO-5046 is a potent, specific and intravenously active inhibitor of neutrophil elastase. To examine the role of elastase in glomerulonephritis, we tested the effects of ONO-5046 on nephrotoxic serum (NTS) nephritis in a rat model of the disease in humans. Rats were administered ONO-5046 or phosphate-buffered saline (PBS) intraperitoneally 24 hours prior to injection of NTS, and they were then given equal doses of ONO-5046 or PBS three hours and 1, 2, 3, 4, 5 and 6 days later. Compared with the control groups, ONO-5046 significantly reduced proteinuria and hematuria, and suppressed the formation of crescentic glomeruli in a dose-dependent manner. Our results suggest that neutrophil elastase participates in NTS nephritis by degrading glomerular basement membrane proteins, and that the elastase inhibitor, ONO-5046, suppresses crescentic formation and glomerular injury caused by elastase.
S Suzuki; F Gejyo; T Kuroda; J J Kazama; N Imai; H Kimura; M Arakawa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Kidney international     Volume:  53     ISSN:  0085-2538     ISO Abbreviation:  Kidney Int.     Publication Date:  1998 May 
Date Detail:
Created Date:  1998-06-30     Completed Date:  1998-06-30     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1201-8     Citation Subset:  IM    
Department of Clinical and Laboratory Medicine, Fukui Medical University, Japan.
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MeSH Terms
Antibodies, Heterophile / administration & dosage
Basement Membrane / immunology
Disease Models, Animal
Glycine / analogs & derivatives*,  pharmacology
Hematuria / prevention & control
Kidney Glomerulus / enzymology,  immunology,  pathology
Leukocyte Elastase / antagonists & inhibitors*,  physiology
Macrophages / pathology
Monocytes / pathology
Nephritis / enzymology*,  pathology,  prevention & control*
Proteinuria / prevention & control
Rats, Inbred WKY
Serine Proteinase Inhibitors / pharmacology*
Sulfonamides / pharmacology*
Reg. No./Substance:
0/Antibodies, Heterophile; 0/Serine Proteinase Inhibitors; 0/Sulfonamides; 127373-66-4/ONO 5046; 56-40-6/Glycine; EC Elastase

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