Document Detail


The cardioprotective efficacy of TVP1022 in a rat model of ischaemia/reperfusion.
MedLine Citation:
PMID:  21323905     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  163     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-27     Completed Date:  2011-10-06     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  755-69     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
Affiliation:
Department of Physiology, Technion-Israel Institute of Technology, Haifa, Israel.
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MeSH Terms
Descriptor/Qualifier:
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:
0/Cardiotonic Agents; 0/Indans; 0/Proto-Oncogene Proteins c-bcl-2; 003N66TS6T/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
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