Abstract | 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:
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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 |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 163
Issue 4
Pg. 755-69
(Jun 2011)
ISSN: 1476-5381 [Electronic] England |
PMID | 21323905
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society. |
Chemical References |
- Cardiotonic Agents
- Indans
- Proto-Oncogene Proteins c-bcl-2
- rasagiline
- Cytochromes c
- Glycogen Synthase Kinase 3 beta
- Gsk3b protein, rat
- Protein Kinase C
- Glycogen Synthase Kinase 3
- Caspase 3
- Caspase 9
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Topics |
- Animals
- Cardiotonic Agents
(pharmacology)
- Caspase 3
(metabolism)
- Caspase 9
(metabolism)
- Cells, Cultured
- Cytochromes c
(metabolism)
- Glycogen Synthase Kinase 3
(metabolism)
- Glycogen Synthase Kinase 3 beta
- 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)
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