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

• Kawai Yoshiko

  Division of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan

• Nakao Takafumi

  Division of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan

• Kunimura Naoshi

  Division of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan

• Kohda Yuka

  Division of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan

• Gemba Munekazu

  Division of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan

Abstract

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-PK₁). Cisplatin at 500 μM significantly increased the production of ROS 5 h and caused cell injury. This agent significantly increased the intracellular calcium level ([Ca²⁺]_i) in a dose-dependent manner 1 h or more after exposure. DPPD (N,N'-diphenyl-p-phenylenediamine), an antioxidant, inhibited a cisplatin-related increase in active oxygen production and cell injury but did not inhibit an early increase in the [Ca²⁺]_i level. An intracellular calcium-chelating compound BAPTA-AM (1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester) inhibited an increase in ROS production and cell injury induced by cisplatin. Furthermore, BAPTA-AM suppressed the rise of [Ca²⁺]_i level in 1 h after exposure; however, an extracellular calcium chelator EGTA and a calcium antagonist nicardipine did not inhibit the rise in [Ca²⁺]_i 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>

Journal

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 100 (1), 65-72, 2006

  The Japanese Pharmacological Society

Keywords

• cisplatin
• nephrotoxicity
• reactive oxygen species
• intracellular calcium
• renal epithelial cell

Details

• CRID: 1390001205175299200
• NII Article ID: 10018241164
• NII Book ID: AA11806667
• DOI: 10.1254/jphs.fp0050661
• ISSN: 13478648
• ISSN: 13478613
• NDL BIB ID: 7783045
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I7783045
• Web Site: https://search.jamas.or.jp/link/ui/2006280755
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
• Abstract License Flag: Disallowed