Erucin Exerts Cardioprotective Effects on Ischemia/Reperfusion Injury through the Modulation of mitoKATP Channels
Lorenzo Flori,
Rosangela Montanaro,
Eleonora Pagnotta,
Luisa Ugolini,
Laura Righetti,
Alma Martelli,
Lorenzo Di Cesare Mannelli,
Carla Ghelardini,
Vincenzo Brancaleone,
Lara Testai,
Vincenzo Calderone
Affiliations
Lorenzo Flori
Department of Pharmacy, University of Pisa, 56120 Pisa, Italy
Rosangela Montanaro
Department of Science, University of Basilicata, 85100 Potenza, Italy
Eleonora Pagnotta
Research Centre for Cereal and Industrial Crops, CREA—Council for Agricultural Research and Economics, Via di Corticella 133, 40128 Bologna, Italy
Luisa Ugolini
Research Centre for Cereal and Industrial Crops, CREA—Council for Agricultural Research and Economics, Via di Corticella 133, 40128 Bologna, Italy
Laura Righetti
Research Centre for Cereal and Industrial Crops, CREA—Council for Agricultural Research and Economics, Via di Corticella 133, 40128 Bologna, Italy
Alma Martelli
Department of Pharmacy, University of Pisa, 56120 Pisa, Italy
Lorenzo Di Cesare Mannelli
Pharmacology and Toxicology Section, Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, 50139 Florence, Italy
Carla Ghelardini
Pharmacology and Toxicology Section, Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, 50139 Florence, Italy
Vincenzo Brancaleone
Department of Science, University of Basilicata, 85100 Potenza, Italy
Lara Testai
Department of Pharmacy, University of Pisa, 56120 Pisa, Italy
Vincenzo Calderone
Department of Pharmacy, University of Pisa, 56120 Pisa, Italy
Modulation of mitochondrial K channels represents a pharmacological strategy to promote cardioprotective effects. Isothiocyanates emerge as molecules capable of releasing hydrogen sulfide (H2S), an endogenous pleiotropic gasotransmitter responsible for anti-ischemic cardioprotective effects also through the involvement of mitoK channels. Erucin (ERU) is a natural isothiocyanate resulting from the enzymatic hydrolysis of glucosinolates (GSLs) present in Eruca sativa Mill. seeds, an edible plant of the Brassicaceae family. In this experimental work, the specific involvement of mitoKATP channels in the cardioprotective effect induced by ERU was evaluated in detail. An in vivo preclinical model of acute myocardial infarction was reproduced in rats to evaluate the cardioprotective effect of ERU. Diazoxide was used as a reference compound for the modulation of potassium fluxes and 5-hydroxydecanoic acid (5HD) as a selective blocker of KATP channels. Specific investigations on isolated cardiac mitochondria were carried out to evaluate the involvement of mitoKATP channels. The results obtained showed ERU cardioprotective effects against ischemia/reperfusion (I/R) damage through the involvement of mitoKATP channels and the consequent depolarizing effect, which in turn reduced calcium entry and preserved mitochondrial integrity.
