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Treatment with an adenosine uptake inhibitor attenuates glomerulonephritis in mice.

Authors
  • Noji, Tohru
  • Sato, Hitoshi
  • Sano, Jun-ichi
  • Nishikawa, Satoshi
  • Kusaka, Hideaki
  • Karasawa, Akira
Type
Published Article
Journal
European Journal of Pharmacology
Publisher
Elsevier
Publication Date
Aug 09, 2002
Volume
449
Issue
3
Pages
293–300
Identifiers
PMID: 12167472
Source
Medline
License
Unknown

Abstract

This study evaluated the effects of KF24345 (3-[1-(6,7-diethoxy-2-morpholinoquinazolin-4-yl)piperidin-4-yl]-1,6-dimethyl-2,4(1H,3H)-quinazolinedione hydrochloride), a novel adenosine uptake inhibitor, on experimental glomerulonephritis induced in mice by two intravenous injections of rabbit anti-mouse glomerular basement membrane antiserum. Mice with glomerulonephritis showed continuous proteinuria and the histological evaluation revealed glomerular and tubular damage at 7 weeks after the first antiserum injection. KF24345 as well as prednisolone and cyclophosphamide significantly inhibited proteinuria and glomerular damage when it was orally administered once a day from 2 to 7 weeks. Prednisolone elevated plasma bilirubin and glutamic-pyruvic transaminase levels, and cyclophosphamide decreased erythrocytes. Moreover, both prednisolone and cyclophosphamide decreased spleen and thymus weights. KF24345 did not show this kind of side effects. These results demonstrate that KF24345 ameliorates glomerulonephritis with minimal side effects in mice, suggesting that the adenosine uptake inhibitor may be useful for the treatment of glomerulonephritis.

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