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The Leukotriene B4 Receptor Antagonist ONO-4057 Inhibits Nephrotoxic Serum Nephritis in WKY Rats

SATORU SUZUKI^*, TAKESHI KURODA, JUN-ICHIROU KAZAMA, NAOFUMI IMAI, HIDEKI KIMURA^*, MASAAKI ARAKAWA and FUMITAKE GEJYO^*

^* Department of Clinical and Laboratory Medicine, Fukui Medical University, Fukui, Japan
Department of Medicine (II), Niigata University School of Medicine, Niigata, Japan.

Correspondence to Dr. Satoru Suzuki, Department of Clinical and Laboratory Medicine, Fukui Medical University, Matsuoka, Fukui, 910-1193 Japan. Phone: 0776-61-3111; Fax: 0776-61-8120; E-mail: ssuzuki{at}fmsrsa.fukui-med.ac.jp

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.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673