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Mechanisms responsible for reduced cardiotoxicity of mitoxantrone compared to doxorubicin examined in isolated guinea-pig heat preparations
http://hdl.handle.net/10659/1818
http://hdl.handle.net/10659/18185ee19d39-8c8a-4a9c-b02c-31d6685c96dd
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
S-536_Uchide.pdf (1.1 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2011-03-31 | |||||
| タイトル | ||||||
| タイトル | Mechanisms responsible for reduced cardiotoxicity of mitoxantrone compared to doxorubicin examined in isolated guinea-pig heat preparations | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| 著者 |
CHUGUN, Akihito
× CHUGUN, Akihito× UCHIDE, Tsuyoshi× TSURIMAKI, Chieko× NAGASAWA, Hajime× SASAKI, Takushi× UENO, Shunji× TAKAGISHI, Kiyohiko× HARA, Yukio× TEMMA, Kyosuke |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | We reported previously that doxorubicin, an anticancer agent that has an anthracycline structure, alters Ca^<2+> 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 Ca^<2+> concentrations ([Ca^<2+>] i), and prolonged the time to peak [Ca^<2+>]i. In skinned muscle fiber preparations obtained from the left ventricular muscle, 30 μM mitoxantrone significantly increased the caffeine-induced contraction without affecting the Ca^<2+> sensitivity of contractile proteins. These results suggest that mitoxantrone enhances Ca^<2+> 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. | |||||
| 書誌情報 |
The journal of veterinary medical science 巻 70, 号 3, p. 255-264, 発行日 2008-03 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0916-7250 | |||||
| DOI | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1292/jvms.70.255 | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| 出版者 | ||||||
| 出版者 | 日本獣医学会 | |||||
| 資源タイプ | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Article | |||||
