The cardioprotective efficacy of TVP1022 in a rat model of ischaemia/reperfusion

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 2O 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 2O 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.

Original languageEnglish
Pages (from-to)755-769
Number of pages15
JournalBritish Journal of Pharmacology
Volume163
Issue number4
DOIs
StatePublished - Jun 2011
Externally publishedYes

Keywords

  • TVP1022
  • cardiomyocytes
  • cardioprotection
  • ischaemia/reperfusion injury
  • myocardial infarction

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