Edaravone, a Potent Free Radical Scavenger, Prevents Anthracycline-Induced Myocardial Cell Death
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概要
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Background It was investigated whether edaravone, a potent free radical scavenger, would protect against anthracycline-induced cardiotoxicity and prevent cardiac function deterioration. Methods and Results Cultured neonatal rat cardiomyocytes were stimulated by daunorubicin 1μmol/L either with or without edaravone or superoxide dismutase mimetic Mn (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP). Cell viability was estimated by measuring the amount of lactate dehydrogenase (LDH) released into the culture medium. Apoptosis was determined by a caspase-3 activity assay and a histone-DNA complex fragment assay. To investigate whether edaravone interfered with daunorubicin's antitumor effect, daunorubicin and edaravone were added to human leukemia K562 cells, and the surviving cells were counted. In addition, edaravone's in vivo effect was evaluated using Sprague-Dawley rats. A total of 15mg/kg doxorubicin was injected intraperitoneally either with or without simultaneous edaravone injection. Two and 6 weeks after the final injection, left ventricular diastolic diameter and left ventricular fraction shortening were assessed echocardiographically. The LDH assay showed that edaravone significantly inhibited LDH release from cardiac myocytes (p=0.0428). The caspase-3 activity and histone-DNA complex fragment assays demonstrated that edaravone's apoptosis suppression effect was much weaker than that of MnTMPyP. The in vivo study showed that edaravone prevented doxorubicin-induced cardiac deterioration. Finally, edaravone was found to not affect daunorubicin's anticancer effect on K562 cells. Conclusions Edaravone protects cardiomyocytes from anthracycline-induced cardiotoxicity via an anti-necrotic rather than an anti-apoptotic effect. (Circ J 2007; 71: 1815-1820)
- 社団法人日本循環器学会の論文
- 2007-10-20
著者
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FUKAZAWA RYUJI
Department of Pediatrics, Nippon Medical School
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OGAWA SHUNICHI
Department of Pediatrics, Nippon Medical School
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WATANABE Makoto
Department of Preventive Cardiology, National Cardiovascular Center
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Ikegami Ei
Department of Pediatrics, Nippon Medical School
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Katsube Yasuhiro
Department ot Pediatrics, Nippon Medical School
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Kamisago Mitsuhiro
Department ot Pediatrics, Nippon Mediccl School
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ABE Masanori
Department of Community Medicine, Ehime University Graduate School of Medicine
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Ogawa Shunichi
Department Of Pediatrics Nippon Medical School
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WATANABE MIKI
Department of Rheumatology and Hematology, Tohoku University School of Medicine
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Hajikano Miharu
Department of Pediatrics, Nippon Medical School
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Ikegami Ei
Department Of Pediatrics Nippon Medical School Hospital
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Ikegami Ei
Department Of Pediatrics Nippon Medical School
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Fukazawa Ryuji
Department Of Pediatrics Nippon Medical School
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Katsube Yasuhiro
Department Of Pediatrics Nippon Medical School
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Kanbe Masaru
Department of Surgery, Cardiovascular Surgery, Nippon Medical School
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Kamisago Mitsuhiro
Department Of Pediatrics Nippon Medical School
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Abe Masanori
Department Of Pediatrics Nippon Medical School
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Watanabe Miki
Department Of Pediatrics Cardiovascular Surgery Nippon Medical School
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Watanabe Makoto
Department Of Cardiology Hirai Hospital
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Hajikano Miharu
Department Of Pediatrics Nippon Medical School
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Katsube Yasuhiro
Department Ot Pediatrics Nippon Medical School
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Kanbe Masaru
Department Of Surgery Cardiovascular Surgery Nippon Medical School
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Abe Masanori
Department Of Anesthesiology Faculty Of Medicine University Of The Ryukyus
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Watanabe Makoto
Department Of Cardiology Anjo Kosei Hospital
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Watanabe Makoto
Department Of Analytical Chemistry Of Medicines. Showa Pharmaceutical University
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Watanabe Makoto
Department of Analytical Chemistry of Medicines, Showa Pharmaceutical University
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