| The cardioprotective efficacy of TVP1022 in a rat model of ischaemia/reperfusion. | |
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MedLine Citation:
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PMID: 21323905 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE: Because myocardial infarction is a major cause of morbidity and mortality worldwide, protecting the heart from the ischaemia and reperfusion (I/R) damage is the focus of intense research. Based on our in vitro findings showing that TVP1022 (the S-enantiomer of rasagiline, an anti-Parkinsonian drug) possesses cardioprotective effects, in the present study we investigated the hypothesis that TVP1022 can attenuate myocardial damage in an I/R model in rats. EXPERIMENTAL APPROACH: The model consisted of 30-min occlusion of the left anterior descending artery followed by 4 or 24 h reperfusion. In addition, we investigated the possible mechanisms of cardioprotection in H9c2 cells and neonatal rat ventricular myocytes (NRVM) exposed to oxidative stress induced by H(2) O(2) . KEY RESULTS: TVP1022 (20 and 40 mg·kg(-1) ) administered 5 min before reperfusion followed by an additional dose 4 h after reperfusion reduced the infarct size and attenuated the decline in ventricular function. TVP1022 also attenuated I/R-induced deterioration in cardiac mitochondrial integrity evaluated by mitochondrial swelling capacity. In vitro, using H9c2 cells and NRVM, TVP1022 attenuated both serum free- and H(2) O(2) -induced damage, preserved mitochondrial membrane potential and Bcl-2 levels, inhibited mitochondrial cytochrome c release and the increase in cleaved caspase 9 and 3 levels, and enhanced the phosphorylation of protein kinase C and glycogen synthase kinase-3β. CONCLUSIONS AND IMPLICATIONS: TVP1022 provided cardioprotection in a model of myocardial infarction, and therefore should be considered as a novel adjunctive therapy for attenuating myocardial damage resulting from I/R injuries. |
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Authors:
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Offir Ertracht; Esti Liani; Noa Bachner-Hinenzon; Orit Bar-Am; Luba Frolov; Elena Ovcharenko; Huda Awad; Shany Blum; Yaron Barac; Tamar Amit; Dan Adam; Moussa Youdim; Ofer Binah |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: British journal of pharmacology Volume: 163 ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-05-27 Completed Date: 2011-10-06 Revised Date: 2012-09-19 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 755-69 Citation Subset: IM |
Copyright Information:
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© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society. |
Affiliation:
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Department of Physiology, Technion-Israel Institute of Technology, Haifa, Israel. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cardiotonic Agents / pharmacology* Caspase 3 / metabolism Caspase 9 / metabolism Cells, Cultured Cytochromes c / metabolism Glycogen Synthase Kinase 3 / metabolism Indans / pharmacology* Male Membrane Potentials / drug effects Mitochondria / drug effects, metabolism Myocardial Infarction / metabolism, prevention & control* Myocardium / metabolism Protein Kinase C / metabolism Proto-Oncogene Proteins c-bcl-2 / metabolism Rats Rats, Sprague-Dawley Reperfusion Injury / metabolism, prevention & control* |
| Chemical | |
Reg. No./Substance:
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0/Cardiotonic Agents; 0/Indans; 0/Proto-Oncogene Proteins c-bcl-2; 1875-50-9/rasagiline; 9007-43-6/Cytochromes c; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.26/Glycogen Synthase Kinase 3; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 9 |
| Comments/Corrections | |
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