title: 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.
authors.affiliation: Department of Clinical and Laboratory Medicine, Fukui Medical University, Matsuoka, Japan. ssuzuki@fmsrsa.fukui-med.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Kuroda
authors.forename: J I
authors.initials: JI
authors.lastname: Kazama
authors.forename: N
authors.initials: N
authors.lastname: Imai
authors.forename: H
authors.initials: H
authors.lastname: Kimura
authors.forename: M
authors.initials: M
authors.lastname: Arakawa
authors.forename: F
authors.initials: F
authors.lastname: Gejyo
mesh_terms: 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*
chemical_list: D007106:Immune Sera; D007166:Immunosuppressive Agents; D010666:Phenylpropionates; D018102:Receptors, Leukotriene B4; C067523:ONO-LB 457