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The Cardioprotective Efficacy of TVP1022 in a Rat Model of ischaemia/reperfusion

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

Br J Pharmacol. 2011 Jun;163(4):755-69.

PMID: 21323905

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:
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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP185517742	TVP1022		185517-74-2	Price

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