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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.
MedLine Citation:
PMID:  23615023     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Mayuko Sakanashi; Toshihiro Matsuzaki; Katsuhiko Noguchi; Junko Nakasone; Makiko Sakanashi; Taro Uchida; Mika Kina-Tanada; Haruaki Kubota; Kumiko Arakaki; Akihide Tanimoto; Nobuyuki Yanagihara; Matao Sakanashi; Yusuke Ohya; Hiroaki Masuzaki; Shogo Ishiuchi; Kazuhiro Sugahara; Masato Tsutsui
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-4-24
Journal Detail:
Title:  Circulation journal : official journal of the Japanese Circulation Society     Volume:  -     ISSN:  1347-4820     ISO Abbreviation:  Circ. J.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-4-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101137683     Medline TA:  Circ J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus.
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