• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2006 Fiscal Year Final Research Report Summary

The elucidation of the mechanisms underlying contrast media induced nephrotoxicity and its prophylaxis.

Research Project

Project/Area Number 17590471
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied pharmacology
Research InstitutionKYUSHU UNIVERCITY

Principal Investigator

OISHI Ryozo  Kyushu University, Hospital, Professor, 大学病院, 教授 (90112325)

Co-Investigator(Kenkyū-buntansha) ITOH Yoshinori  Gifu University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (50159927)
Project Period (FY) 2005 – 2006
Keywordscontrast media / nephrotoxicity / apoptosis / ceramide / cyclic AMP / prostacyclin
Research Abstract

Radiographic contrast medium (RCM) is one of major causes of drug-induced acute renal failure, although the cellular mechanisms are not fully understood. We investigated that RCM induces apoptosis in renal tubular cells, in which decrease in bcl-2 mRNA and subsequent activation of caspase-9 and caspase-3 are involved. Moreover, RCM-induced reduction in Bcl-2 expression was found to be mediated by decrease in phosphorylated Akt (pAkt) and cyclic AMP (cAMP)-responsive element binding protein (CREB) phosphorilation. Various RCM increased ceramide content in renal tubular cells, in which the increase was closely related to the loss of cell viability. Both the elevation of ceramide content and cell injury induced by RCM were reversed by fumonisin Bl but not D609, suggesting a role for de novo ceramide synthesis. Like RCM, ceramide decreased pAkt, reduced Bcl-2 expression, enhanced caspase-9 and caspase-3 activities, and led to apoptosis. The protective effect of fumonisin Bl was also observed in vivo in murine model of RCM nephropathy. Moreover, a prostacyclin analog beraprost induce the elevation of endogenous cAMP effectively prevents radiocontrast nephropathy, in which activation of A kinase/PI 3-kinase/Akt followed by CREB phosphorylation are involved.
These findings suggest that ceramide synthesis inhibitor or beraprost may be potentially useful for the prophylaxis of radiographic contrast media nephrotoxicity.

  • Research Products

    (6 results)

All 2006 2005

All Journal Article (6 results)

  • [Journal Article] Involvement of de novo ceramide synthesis in radiocontrast-induced renal tubular cell injury.2006

    • Author(s)
      Itoh Y, Yano T, Sendo T, Sueyasu M, Hirano K, Kanaide H, Oishi R
    • Journal Title

      Kidney International 69

      Pages: 288-297

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Involvement of de novo ceramide synthesis in radiocontrast-induced renal tubular cell injury.2006

    • Author(s)
      Itoh Y, Yano T, Sendo T, Sueyasu M, Hirano K, Kanaide H, Oishi R.
    • Journal Title

      Kidney International 69

      Pages: 288-297

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Clinical and experimental evidence for prevention of acute renal failure induced by radiographic contrast media.2005

    • Author(s)
      Itoh Y, Yano T, Sendo T, Oishi R
    • Journal Title

      Journal of Pharmacological Sciences 97

      Pages: 473-488

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A prostacyclin analog prevents radiocontrast nephropathy via phosphorylation of cyclic AMP response element binding protein.2005

    • Author(s)
      Yano T, Itoh Y, Kubota T, Sendo T, Koyama T, Fujita T, Saeki K, Yuo A, Oishi R
    • Journal Title

      American Journal of Pathology 166

      Pages: 1333-1342

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A prostacyclin analog prevents radiocontrast nephropathy via phosphorylation of cyclic AMP response element binding protein.2005

    • Author(s)
      Yano T, Itoh Y, Kubota T, Sendo T, Koyama T, Fujita T, Saeki K, Yuo A, Oishi R.
    • Journal Title

      American Journal of Pathology 166

      Pages: 1333-1342

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Clinical and experimental evidence for prevention of acute renal failure induced by radiographic contrast media.2005

    • Author(s)
      Itoh Y, Yano T, Sendo T, Oishi R.
    • Journal Title

      Journal of Pharmacological Sciences 97

      Pages: 473-488

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2008-05-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi