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The leukotriene B4 receptor antagonist ONO-4057 inhibits nephrotoxic serum nephritis in WKY rats.

Abstract
To evaluate the role of leukotriene B4 (LTB4) in glomerulonephritis, this study was conducted to examine whether ONO-4057, an LTB4 receptor antagonist, moderated nephritis caused by the injection of nephrotoxic serum (NTS) into Wistar-Kyoto rats. Rats were given intraperitoneal injections of ONO-4057 or phosphate-buffered saline 24 h before the injection of NTS. These rats subsequently received equal doses of ONO-4057 or phosphate-buffered saline 3 h and 1, 2, 3, 4, 5, and 6 d later. Compared with the control groups, ONO-4057 treatment significantly reduced proteinuria and hematuria, suppressed the glomerular accumulation of monocytes/macrophages, and reduced the formation of crescentic glomeruli in a dose-dependent manner. These results suggest that LTB4 is responsible for the crescentic formations and renal dysfunction associated with NTS nephritis. The LTB4 receptor antagonist ONO-4057 may thus be beneficial in the treatment of crescentic glomerulonephritis.
AuthorsS Suzuki, T Kuroda, J I Kazama, N Imai, H Kimura, M Arakawa, F Gejyo
JournalJournal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 10 Issue 2 Pg. 264-70 (Feb 1999) ISSN: 1046-6673 [Print] United States
PMID10215325 (Publication Type: Journal Article)
Chemical References
  • Immune Sera
  • Immunosuppressive Agents
  • Phenylpropionates
  • Receptors, Leukotriene B4
  • ONO-LB 457
Topics
  • Animals
  • Dose-Response Relationship, Drug
  • Glomerulonephritis (immunology, pathology, prevention & control, urine)
  • Hematuria (urine)
  • Immune Sera (immunology)
  • Immunohistochemistry
  • Immunosuppressive Agents (pharmacology)
  • Kidney Glomerulus (drug effects, pathology)
  • Male
  • Phenylpropionates (pharmacology)
  • Proteinuria (urine)
  • Rats
  • Rats, Inbred WKY
  • Receptors, Leukotriene B4 (antagonists & inhibitors)

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