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

J Am Soc Nephrol. 1999 Feb;10(2):264-70. doi: 10.1681/ASN.V102264.

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.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Glomerulonephritis / immunology*
  • Glomerulonephritis / pathology
  • Glomerulonephritis / prevention & control*
  • Glomerulonephritis / urine
  • Hematuria / urine
  • Immune Sera / immunology*
  • Immunohistochemistry
  • Immunosuppressive Agents / pharmacology*
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / pathology
  • Male
  • Phenylpropionates / pharmacology*
  • Proteinuria / urine
  • Rats
  • Rats, Inbred WKY
  • Receptors, Leukotriene B4 / antagonists & inhibitors*

Substances

  • Immune Sera
  • Immunosuppressive Agents
  • Phenylpropionates
  • Receptors, Leukotriene B4
  • ONO-LB 457