Relationship of Intracellular Calcium and Oxygen Radicals to Cisplatin-Related Renal Cell Injury
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概要
- 論文の詳細を見る
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.
- 社団法人 日本薬理学会の論文
- 2006-01-20
著者
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Nakao Takafumi
Division Of Pharmacology Osaka University Of Pharmaceutical Sciences
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Kohda Yuka
Laboratory Of Pharmacology Osaka University Of Pharmaceutical Sciences
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Kawai Yoshiko
Laboratory Of Pharmacology Osaka University Of Pharmaceutical Sciences
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Kohda Yuka
Division Of Pharmacology Osaka University Of Pharmaceutical Sciences
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Kawai Yoshiko
Division Of Pharmacology Osaka University Of Farmaceutical Sciences
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Gemba Munekazu
Laboratory Of Functional Morphology Yokohama College Of Pharmacy
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Gemba M
Osaka Univ. Pharmaceutical Sci. Osaka Jpn
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Gemba Munekazu
Division Of Pharmacology Osaka University Of Pharmaceutical Sciences
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KUNIMURA Naoshi
Division of Pharmacology, Osaka University of Pharmaceutical Sciences
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Gemba Munekazu
Division Of Pharmacology Osaka University Of Farmaceutical Sciences
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Kunimura Naoshi
Division Of Pharmacology Osaka University Of Pharmaceutical Sciences
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