モルモット摘出心筋標本におけるミトキサントロンのドキソルビシンと比較した低心毒性作用の機序

• CHUGUN Akihito

  Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University

• UCHIDE Tsuyoshi

  Laboratory of Toxicology, School of Veterinary Medicine, Kitasato University

• TSURIMAKI Chieko

  Laboratory of Toxicology, School of Veterinary Medicine, Kitasato University

• NAGASAWA Hajime

  Laboratory of Toxicology, School of Veterinary Medicine, Kitasato University

• SASAKI Takushi

  Laboratory of Toxicology, School of Veterinary Medicine, Kitasato University

• UENO Shunji

  Laboratory of Veterinary Public Health, School of Veterinary Medicine, Kitasato University

• TAKAGISHI Kiyohiko

  Laboratory of Cell and Molecular Biology, School of Veterinary Medicine, Kitasato University

• HARA Yukio

  Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University

• TEMMA Kyosuke

  Laboratory of Toxicology, School of Veterinary Medicine, Kitasato University

書誌事項

タイトル別名

• Mechanisms Responsible for Reduced Cardiotoxicity of Mitoxantrone Compared to Doxorubicin Examined in Isolated Guinea-Pig Heart Preparations
• Toxicology: Mechanisms responsible for reduced cardiotoxicity of mitoxantrone compared to doxorubicin examined in isolated guinea-pig heart preparations

抄録

We reported previously that doxorubicin, an anticancer agent that has an anthracycline structure, alters Ca²⁺ releasing and uptake mechanisms in the sarcoplasmic reticulum of myocardial cells. These effects of doxorubicin are apparently related to its cardiotoxicity. Mitoxantrone is a similar anticancer agent with an anthracenedion structure that has been shown to be significantly less cardiotoxic. In the present study, the effects of mitoxantrone on the functions of the sarcoplasmic reticulum were examined in isolated muscle preparations obtained from the guinea-pig heart. In electrically-stimulated left atrial muscle preparations, incubation in vitro for 4 hr with 30 or 100 μM mitoxantrone significantly prolonged the time to the peak of twitch tension, markedly increased the developed tension observed at lower stimulation frequencies, thereby attenuating the slope of positive force-frequency relationships, and increased the postrest contraction observed after a 60-sec quiescent period. In myocytes isolated from ventricular muscles, 30 μM mitoxantrone increased the peak and the size of intracellular Ca²⁺ concentrations ([Ca²⁺] i), and prolonged the time to peak [Ca²⁺]i. In skinned muscle fiber preparations obtained from the left ventricular muscle, 30 μM mitoxantrone significantly increased the caffeine-induced contraction without affecting the Ca²⁺ sensitivity of contractile proteins. These results suggest that mitoxantrone enhances Ca²⁺ release from the sarcoplasmic reticulum in isolated atrial muscle preparations obtained from the guinea-pig heart. Apparent enhancement of the sarcoplasmic reticulum functions, in contrast to anthracyclines that has been shown to suppress these functions, seems to explain the relative lack of marked cardiotoxicity of mitoxantrone.<br>

収録刊行物

• Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｖｅｔｅｒｉｎａｒｙ　Ｍｅｄｉｃａｌ　Ｓｃｉｅｎｃｅ

  Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｖｅｔｅｒｉｎａｒｙ　Ｍｅｄｉｃａｌ　Ｓｃｉｅｎｃｅ 70 (3), 255-264, 2008

  公益社団法人 日本獣医学会

キーワード

• caffeine-induced contraction
• Ca²⁺ release and uptake by sarcoplasmic reticulum
• inotropic effects
• intracellular Ca²⁺ concentration
• mitoxantrone

詳細情報

• CRID: 1390282681404721664
• NII論文ID: 110006633671
• NII書誌ID: AA10796138
• DOI: 10.1292/jvms.70.255
• ISSN: 13477439
• ISSN: 09167250
• NDL書誌ID: 9438949
• Web Site: https://agriknowledge.affrc.go.jp/RN/2010761017
• Web Site: http://id.ndl.go.jp/bib/9438949
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I9438949
• Web Site: http://www.jstage.jst.go.jp/article/jvms/70/3/70_3_255/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2008168334
• 本文言語コード: en
• データソース種別:
  • JaLC
  • IRDB
  • NDL
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可