The leukotriene B4 receptor antagonist ONO-4057 inhibits nephrotoxic serum nephritis in WKY rats.
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.
Suzuki
S
S
Department of Clinical and Laboratory Medicine, Fukui Medical University, Matsuoka, Japan. ssuzuki@fmsrsa.fukui-med.ac.jp
Kuroda
T
T
Kazama
J I
JI
Imai
N
N
Kimura
H
H
Arakawa
M
M
Gejyo
F
F
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control* / Q000652:urine; D006417:Hematuria / Q000652:urine; D007106:Immune Sera / Q000276:immunology*; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D008297:Male; D010666:Phenylpropionates / Q000494:pharmacology*; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011921:Rats, Inbred WKY; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors*
D007106:Immune Sera; D007166:Immunosuppressive Agents; D010666:Phenylpropionates; D018102:Receptors, Leukotriene B4; C067523:ONO-LB 457