Elucidation of the mechanism in cisplatin-induced renal failure anddevelopment of drug therapy aimed at the mitigation of the renal toxicity of cisplatin.

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590251
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Hyogo University of Health Sciences
• Principal Investigator: UEDA Haruyasu 兵庫医療大学, 薬学部, 准教授 (10330458)
• Co-Investigator(Kenkyū-buntansha): TANAKA Toshiyuki 兵庫医療大学, 薬学部, 教授 (30217054) ; OONO Yoshiya 兵庫医療大学, 薬学部, 助教 (40509155)
• Project Period (FY): 2010 – 2012
• Keywords: 炎症・免疫 / サイトカイン

Research Abstract

Cisplatin is a chemotherapeutic agent having a potent anti-tumor effect. However, in some cases, cisplatin has often withdrawn due to renal toxicity. Therefore, we tried to elucidate mechanisms involved in renal toxicity of cisplatin, and find out therapy to improve it, and thus, it might be able to reduce the nephrotoxicity without disturbing the anticancer effect of cisplatin by combination with drugs to elucidate mechanisms involved in renal toxicity of cisplatin. In the present research, we have proposed a novel mechanism(s) on the development of cisplatin-induced renal failure that cisplatin accelerates chymase-dependent production of IL-18 which stimulates aldosterone synthesis, and that extended excretion of cisplatin causes renal inflammation. Thus, concomitant use of inhibitor(s) of chymase activity or aldosteron binding to its receptor with cisplatin could be reducing the pathogenesis of renal damage by cisplatin therapy.

Research Products

• [Journal Article] Cisplatin-induced acute renal failure in mice is mediated by chymase-activated angiotensin-aldosterone system and interleukin-18 Eur. (2012)
  • Author(s): Okui, S., Yamamoto, H., Li, W., Gamachi,N., Fujita, Y., Kashiwamura, S., Miura, D., Takai, S., Miyazaki, M., Urade, M.,Okamura, H., Ueda, H.
  • Journal Title: J. Pharmacol. Volume: 685 Pages: 149-155
  • Peer Reviewed