Relationship of Intracellular Calcium and Oxygen Radicals to Cisplatin-Related Renal Cell Injury

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We investigated the involvement of reactive oxygen species (ROS) and intracellular calcium in nephrotoxicity related to an antitumor agent, cisplatin. In this study, we employed cultured renal epithelial cells (LLC-PK<sub>1</sub>). Cisplatin at 500 μM significantly increased the production of ROS 5 h and caused cell injury. This agent significantly increased the intracellular calcium level ([Ca<sup>2+</sup>]<sub>i</sub>) in a dose-dependent manner 1 h or more after exposure. DPPD (<i>N</i>,<i>N'</i>-diphenyl-<i>p</i>-phenylenediamine), an antioxidant, inhibited a cisplatin-related increase in active oxygen production and cell injury but did not inhibit an early increase in the [Ca<sup>2+</sup>]<sub>i</sub> level. An intracellular calcium-chelating compound BAPTA-AM (1,2-bis(<i>O</i>-aminophenoxy)ethane-<i>N</i>,<i>N</i>,<i>N'</i>,<i>N'</i>-tetraacetic acid tetra(acetoxymethyl) ester) inhibited an increase in ROS production and cell injury induced by cisplatin. Furthermore, BAPTA-AM suppressed the rise of [Ca<sup>2+</sup>]<sub>i</sub> level in 1 h after exposure; however, an extracellular calcium chelator EGTA and a calcium antagonist nicardipine did not inhibit the rise in [Ca<sup>2+</sup>]<sub>i</sub> level in the early phase. An NADPH oxidase inhibitor inhibited a cisplatin-related increase in ROS production and cell disorder. These results suggest that cisplatin-related calcium release from the site of intracellular calcium storage in the early phase causes oxidative stress in renal tubular epithelial cells. Cisplatin may increase the intracellular production of ROS via NADPH oxidase.<br>

収録刊行物

  • Journal of pharmacological sciences  

    Journal of pharmacological sciences 100(1), 65-72, 2006-01-20 

    The Japanese Pharmacological Society

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各種コード

  • NII論文ID(NAID)
    10018241164
  • NII書誌ID(NCID)
    AA11806667
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    13478613
  • NDL 記事登録ID
    7783045
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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