Evaluation of the cardioprotective properties of novel synthetic and natural agents in an acute myocardial infarct model and investigation of the mitochondrial targets.

Mitochondria play a crucial role in the mechanisms of cell death during events of acute myocardial infarction and in the protective mechanisms at the basis of ischemic conditioning. Therefore, these organelles have been studied in great detail, in order to develop mitochondrial drugs able to act on cardioprotective signalling pathways. Particularly the mitochondrial potassium channels play a fundamental role in these processes, being final effectors of ischemic conditioning, therefore represent a main pharmacological target to obtain a cytoprotective effects. In this thesis, the cardioprotective effects of two drugs were studied, in an in vivo model of ischemia/reperfusion. The first drug tested, Vek-33, is a synthetic derivative, obtained through the conjugation of Tetraphenyl phosphonium (TPP+) with Isosteviol to optimize the delivery of this molecule inside the mitochondria. Indeed, Isosteviol is a diterpenoid obtained from Stevia rebaudiana, which showed cardioprotective activity in previous studies. Then the cardioprotective effect of an extract of Eruca sativa Mill., containing Glucoerucin (95%) and Glucoraphanin (5%), has been evaluated. Noteworthy Glucoerucin and Glucoraphanin are two natural glucosinolates, that in the presence of myrosinase enzymes, can be converted into related isothiocyanates (Erucin and Sulforaphanine) which in turn relase H2S. H2S is an endogenous gastrasmitter which promotes several beneficial effects in particular in the cardiovascular system. In order to investigate the mechanism of action of the extract, we selected Glucoerucin and its derivative Erucin and their effect on the mitochondrial membrane potential has been evaluated