PMID- 10906168 OWN - NLM STAT- MEDLINE DCOM- 20000908 LR - 20210511 IS - 1046-6673 (Print) IS - 1046-6673 (Linking) VI - 11 IP - 8 DP - 2000 Aug TI - A new anti-inflammatory compound, FR167653, ameliorates crescentic glomerulonephritis in Wistar-Kyoto rats. PG - 1534-1541 LID - 10.1681/ASN.V1181534 [doi] AB - The pathophysiologic effects of FR167653 were investigated in a model of crescentic glomerulonephritis induced by a small dose of nephrotoxic serum in Wistar-Kyoto rats. The rats developed crescentic glomerulonephritis by 6 d after the administration of serum. The subcutaneous administration of FR167653 (32 mg/kg) markedly decreased the severity of the renal damage. In a group of rats treated with FR167653 daily from day 0 to day 6, glomerular damage, including crescent formation and proteinuria, was virtually absent. FR167653 markedly decreased urinary levels of monocyte chemoattractant protein-1 (MCP-1). In addition, FR167653 reduced production of MCP-1 protein and transcripts in the diseased kidneys. In a group of rats for which treatment was initiated on day 3, shortly after the appearance of glomerular abnormalities, the progression of renal disease was appreciably retarded, with partial inhibition of MCP-1. In contrast, when rats were treated only on the first day, no beneficial effects were observed and severe proliferative and necrotizing glomerulonephritis, with crescent formation, was induced by day 6, with the upregulation of MCP-1. These results suggest that FR167653 may be effective against crescentic glomerulonephritis, possibly via the inhibition of MCP-1. In addition, there was marked reduction in renal injury even when FR167653 treatment was initiated after glomerular inflammation was established, suggesting that the therapeutic application of FR167653 may be clinically useful for human renal diseases. FAU - Wada, Takashi AU - Wada T AD - First Department of Internal Medicine and Division of Blood Purification, School of Medicine, Kanazawa University, Kanazawa, Japan. FAU - Furuichi, Kengo AU - Furuichi K AD - First Department of Internal Medicine and Division of Blood Purification, School of Medicine, Kanazawa University, Kanazawa, Japan. FAU - Sakai, Norihiko AU - Sakai N AD - First Department of Internal Medicine and Division of Blood Purification, School of Medicine, Kanazawa University, Kanazawa, Japan. FAU - Iwata, Yasunori AU - Iwata Y AD - First Department of Internal Medicine and Division of Blood Purification, School of Medicine, Kanazawa University, Kanazawa, Japan. FAU - Yoshimoto, Keiichi AU - Yoshimoto K AD - First Department of Internal Medicine and Division of Blood Purification, School of Medicine, Kanazawa University, Kanazawa, Japan. FAU - Shimizu, Miho AU - Shimizu M AD - First Department of Internal Medicine and Division of Blood Purification, School of Medicine, Kanazawa University, Kanazawa, Japan. FAU - Kobayashi, Ken-Ichi AU - Kobayashi KI AD - First Department of Internal Medicine and Division of Blood Purification, School of Medicine, Kanazawa University, Kanazawa, Japan. FAU - Mukaida, Naofumi AU - Mukaida N AD - Department of Molecular Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. FAU - Matsushima, Kouji AU - Matsushima K AD - Department of Molecular Preventive Medicine, School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Yokoyama, Hitoshi AU - Yokoyama H AD - First Department of Internal Medicine and Division of Blood Purification, School of Medicine, Kanazawa University, Kanazawa, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Am Soc Nephrol JT - Journal of the American Society of Nephrology : JASN JID - 9013836 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Chemokine CCL2) RN - 0 (FR 167653) RN - 0 (Pyrazoles) RN - 0 (Pyridines) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology MH - Chemokine CCL2/antagonists & inhibitors/biosynthesis/genetics/urine MH - Glomerulonephritis/*pathology/*physiopathology/urine MH - Male MH - Proteinuria/urine MH - Pyrazoles/*pharmacology MH - Pyridines/*pharmacology MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Inbred WKY EDAT- 2000/07/25 11:00 MHDA- 2000/09/19 11:01 CRDT- 2000/07/25 11:00 PHST- 2000/07/25 11:00 [pubmed] PHST- 2000/09/19 11:01 [medline] PHST- 2000/07/25 11:00 [entrez] AID - 11/8/1534 [pii] AID - 10.1681/ASN.V1181534 [doi] PST - ppublish SO - J Am Soc Nephrol. 2000 Aug;11(8):1534-1541. doi: 10.1681/ASN.V1181534.