Cytoprotective Effect of 3-[2-[4-(3-Chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole Dihydrochloride 3.5 Hydrate (DY-9760e) Against Ischemia/Reperfusion-Induced Injury in Rat Heart Involves Inhibition of Fodrin
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概要
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We here assessed the effects of 3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate (DY-9760e), a novel calmodulin antagonist, on infarct size in the rat heart subjected to ischemia/reperfusion. Rats were subjected to a 30-min coronary occlusion followed by a 24-h reperfusion. DY-9760e was intravenously infused for 20 min, starting at 20 min after coronary occlusion. Treatment with DY-9760e (10 mg/kg) significantly reduced the infarct size in the risk area assessed by Evans Blue/TTC (triphenyltetrazolium chloride) staining. DY-9760e treatment also ameliorated contractile dysfunction of the left ventricle 72 h after reperfusion. DY-9760e significantly inhibited fodrin breakdown and caspase-3 activation. The inhibitory effect of DY-9760e on the fodrin breakdown was prominent in the rim rather than in the center of the risk area. DY-9760e also blocked protein tyrosine nitration associated with infarction. These results suggest that the cardioprotective effect of DY-9760e involved inhibition of calpain/caspase activation and protein tyrosine nitration.
- 社団法人 日本薬理学会の論文
- 2005-06-20
著者
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Fukunaga Kohji
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan
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KASAHARA Jiro
Department of Mechanical Systems Engineering, Muroran Institute of Technology
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Takeuchi Yusuke
Department Of Pharmacology Tohoku University Graduate School Of Pharmaceutical Sciences
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Fukunaga Kohji
Tohoku Univ. 21st Century Coe Program “crescendo" Jpn
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Fukunaga K
Department Of Pharmacology Graduate School Of Pharmaceutical Sciences Tohoku University
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Fukunaga Kohji
Department Of Pharmacology Graduate School Of Pharmaceutical Sciences Tohoku University
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SHIRASAKI Yasufumi
New Product Research Laboratories II, Daiichi Pharmaceutical Co., Ltd.
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Hisa Hiroaki
Department Of Pharmacology Tohoku University Graduate School Of Pharmaceutical Sciences
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Hisa Hiroaki
Department Of Pharmacology Pharmaceutical Institute Tohoku University
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Kasahara Jiro
Department Of Pharmacology Tohoku University Graduate School Of Pharmaceutical Sciences
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Kasahara Jiro
Department Of Aerospace Engineering Nagoya University
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TAKADA Yoko
Department of Pharmacology, Niigata College of Pharmacy
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Takada Yoko
Department Of Pharmacology Tohoku University Graduate School Of Pharmaceutical Sciences
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Takada Yoko
Department Of Applied Chemistry Faculty Of Science And Engineering Kinki University
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HASHIMITO Masami
Department of Pharmacology, Tohoku University Graduate School of Pharmaceutical Sciences
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Hashimito Masami
Department Of Pharmacology Tohoku University Graduate School Of Pharmaceutical Sciences
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Shirasaki Yasufumi
New Product Research Laboratories Ii Daiichi Pharmaceutical Co. Ltd.
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Shirasaki Yasufumi
New Product Research Laboratories Ii Daiichi Pharmaceutical
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Hashimoto Masami
Department of Pharmacology, Tohoku University Graduate School of Pharmaceutical Sciences
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