Long-Term Treatment With San'o-Shashin-To, a Kampo Medicine, Markedly Ameliorates Cardiac Ischemia-Reperfusion Injury in Ovariectomized Rats via the Redox-Dependent Mechanism
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概要
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Background: Hormone replacement therapy has failed to reduce ischemic cardiovascular events in climacteric women. To explore alternative therapy, we examined whether san'o-shashin-to (TJ-113), a kampo medicine, ameliorates cardiac ischemia-reperfusion (IR) injury in a climacteric rat model. Methods and Results: Cardiac function and infarct size after IR were significantly exacerbated in ovariectomized rats as compared with sham-operated rats, whereas long-term treatment with a clinical dosage of TJ-113 for 4 weeks markedly improved these functional and morphological changes. Myocardial inducible nitric oxide synthase (iNOS) expression and peroxynitrite levels were significantly higher in ovariectomized rats compared with sham-operated rats, and long-term TJ-113 treatment significantly reduced these oxidative changes. Furthermore, myocardial manganese superoxide dismutase (Mn-SOD) activity was significantly lower in ovariectomized than in sham-operated rats, and long-term TJ-113 treatment significantly restored antioxidant activity. Importantly, those beneficial actions of TJ-113 were significantly inhibited by the estrogen receptor antagonist, fulvestrant, and the phytoestrogen, emodin, a TJ-113 ingredient, mimicked the actions of TJ-113, suggesting involvement of emodin in the effects of TJ-113. Conclusions: These results provide the first evidence that long-term treatment with a clinical dosage of TJ-113 markedly ameliorates cardiac IR injury in ovariectomized rats via inhibition of iNOS expression, suppression of peroxynitrite formation, and restoration of Mn-SOD activity. TJ-113 may be a novel therapeutic option in the treatment of ischemic heart disease in climacteric women.
著者
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Ohya Yusuke
Third Deartment of Internal Medicine, Faculty of Medicine, University of The Ryukyus
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Nakasone Junko
Department Of Pharmacology School Of Medicine Faculty Of Medicine University Of The Ryukyus
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Yanagihara Nobuyuki
Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health
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Ishiuchi Shogo
Department Of Neurosurgery Faculty Of Medicine University Of Ryukyus
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Sugahara Kazuhiro
Department Of Anesthesio1ogy Kumamoto University Medical School
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Noguchi Katsuhiko
Department Of Pharmacalogy School Of Medicine Faculty Of Medicine University Of The Ryukyus
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Yanagihara Nobuyuki
Department Of Phamacology University Of Occupational And Environmental Health
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Sakanashi Matao
Department Of Pharmacology And Department Of Pediatrics School Of Medicine University Of The Ryukyus
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Sakanashi Makiko
Department Of Anesthesiology And Pediatrics University Of The Ryukyus Faculty Of Medicine
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Matsuzaki Toshihiro
Department Of Pharmacology School Of Medicine Faculty Of Medicine University Of The Ryukyus
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Tanimoto Akihide
Department Of Molecular And Cellular Pathology Kagoshima University Graduate School Of Medical And D
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Sakanashi Mayuko
Department Of Pharmacology Graduate School Of Medicine University Of The Ryukyus
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Masuzaki Hiroaki
Second Department Of Internal Medicine Endocrinology Diabetes And Metabolism Hematology And Rheumatology University Of The Ryukyus Graduate School Of Medicine
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Tanimoto Akihide
Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences
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TSUTSUI Masato
Department of Cardiology, Iizuka Hospital
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Sakanashi Matao
Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus
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Sakanashi Makiko
Department of Anesthesiology, Graduate School of Medicine, University of the Ryukyus
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Uchida Taro
Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus
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Kina-Tanada Mika
Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus
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Kubota Haruaki
Department of Anesthesiology, Graduate School of Medicine, University of the Ryukyus
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Arakaki Kumiko
Third, Departments of Internal Medicine, Graduate School of Medicine, University of the Ryukyus
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Ishiuchi Shogo
Department of Neurosurgery, Graduate School of Medicine, University of the Ryukyus
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Ohya Yusuke
Third, Departments of Internal Medicine, Graduate School of Medicine, University of the Ryukyus
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Nakasone Junko
Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus
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Noguchi Katsuhiko
Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus
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