Erucin Exerts Cardioprotective Effects on Ischemia/Reperfusion Injury through the Modulation of mitoKATP Channels

Modulation of mitochondrial K channels represents a pharmacological strategy to promote cardioprotective effects. Isothiocyanates emerge as molecules capable of releasing hydrogen sulfide (H<sub>2</sub>S), an endogenous pleiotropic gasotransmitter responsible for anti-ischemic cardioprot...

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Main Authors: Lorenzo Flori, Rosangela Montanaro, Eleonora Pagnotta, Luisa Ugolini, Laura Righetti, Alma Martelli, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Vincenzo Brancaleone, Lara Testai, Vincenzo Calderone
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/11/12/3281
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author Lorenzo Flori
Rosangela Montanaro
Eleonora Pagnotta
Luisa Ugolini
Laura Righetti
Alma Martelli
Lorenzo Di Cesare Mannelli
Carla Ghelardini
Vincenzo Brancaleone
Lara Testai
Vincenzo Calderone
author_facet Lorenzo Flori
Rosangela Montanaro
Eleonora Pagnotta
Luisa Ugolini
Laura Righetti
Alma Martelli
Lorenzo Di Cesare Mannelli
Carla Ghelardini
Vincenzo Brancaleone
Lara Testai
Vincenzo Calderone
author_sort Lorenzo Flori
collection DOAJ
description Modulation of mitochondrial K channels represents a pharmacological strategy to promote cardioprotective effects. Isothiocyanates emerge as molecules capable of releasing hydrogen sulfide (H<sub>2</sub>S), 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 <i>Eruca sativa</i> Mill. seeds, an edible plant of the <i>Brassicaceae</i> family. In this experimental work, the specific involvement of mitoK<sub>ATP</sub> 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 K<sub>ATP</sub> channels. Specific investigations on isolated cardiac mitochondria were carried out to evaluate the involvement of mitoK<sub>ATP</sub> channels. The results obtained showed ERU cardioprotective effects against ischemia/reperfusion (I/R) damage through the involvement of mitoK<sub>ATP</sub> channels and the consequent depolarizing effect, which in turn reduced calcium entry and preserved mitochondrial integrity.
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spelling doaj.art-8e567d5631784c1c9c6073e4309f3f892023-12-22T13:55:11ZengMDPI AGBiomedicines2227-90592023-12-011112328110.3390/biomedicines11123281Erucin Exerts Cardioprotective Effects on Ischemia/Reperfusion Injury through the Modulation of mitoKATP ChannelsLorenzo Flori0Rosangela Montanaro1Eleonora Pagnotta2Luisa Ugolini3Laura Righetti4Alma Martelli5Lorenzo Di Cesare Mannelli6Carla Ghelardini7Vincenzo Brancaleone8Lara Testai9Vincenzo Calderone10Department of Pharmacy, University of Pisa, 56120 Pisa, ItalyDepartment of Science, University of Basilicata, 85100 Potenza, ItalyResearch Centre for Cereal and Industrial Crops, CREA—Council for Agricultural Research and Economics, Via di Corticella 133, 40128 Bologna, ItalyResearch Centre for Cereal and Industrial Crops, CREA—Council for Agricultural Research and Economics, Via di Corticella 133, 40128 Bologna, ItalyResearch Centre for Cereal and Industrial Crops, CREA—Council for Agricultural Research and Economics, Via di Corticella 133, 40128 Bologna, ItalyDepartment of Pharmacy, University of Pisa, 56120 Pisa, ItalyPharmacology and Toxicology Section, Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, 50139 Florence, ItalyPharmacology and Toxicology Section, Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, 50139 Florence, ItalyDepartment of Science, University of Basilicata, 85100 Potenza, ItalyDepartment of Pharmacy, University of Pisa, 56120 Pisa, ItalyDepartment of Pharmacy, University of Pisa, 56120 Pisa, ItalyModulation of mitochondrial K channels represents a pharmacological strategy to promote cardioprotective effects. Isothiocyanates emerge as molecules capable of releasing hydrogen sulfide (H<sub>2</sub>S), 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 <i>Eruca sativa</i> Mill. seeds, an edible plant of the <i>Brassicaceae</i> family. In this experimental work, the specific involvement of mitoK<sub>ATP</sub> 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 K<sub>ATP</sub> channels. Specific investigations on isolated cardiac mitochondria were carried out to evaluate the involvement of mitoK<sub>ATP</sub> channels. The results obtained showed ERU cardioprotective effects against ischemia/reperfusion (I/R) damage through the involvement of mitoK<sub>ATP</sub> channels and the consequent depolarizing effect, which in turn reduced calcium entry and preserved mitochondrial integrity.https://www.mdpi.com/2227-9059/11/12/3281erucinisothiocyanatesmitochondrial channelsmitoK<sub>ATP</sub> channelsH<sub>2</sub>SH<sub>2</sub>S donors
spellingShingle Lorenzo Flori
Rosangela Montanaro
Eleonora Pagnotta
Luisa Ugolini
Laura Righetti
Alma Martelli
Lorenzo Di Cesare Mannelli
Carla Ghelardini
Vincenzo Brancaleone
Lara Testai
Vincenzo Calderone
Erucin Exerts Cardioprotective Effects on Ischemia/Reperfusion Injury through the Modulation of mitoKATP Channels
Biomedicines
erucin
isothiocyanates
mitochondrial channels
mitoK<sub>ATP</sub> channels
H<sub>2</sub>S
H<sub>2</sub>S donors
title Erucin Exerts Cardioprotective Effects on Ischemia/Reperfusion Injury through the Modulation of mitoKATP Channels
title_full Erucin Exerts Cardioprotective Effects on Ischemia/Reperfusion Injury through the Modulation of mitoKATP Channels
title_fullStr Erucin Exerts Cardioprotective Effects on Ischemia/Reperfusion Injury through the Modulation of mitoKATP Channels
title_full_unstemmed Erucin Exerts Cardioprotective Effects on Ischemia/Reperfusion Injury through the Modulation of mitoKATP Channels
title_short Erucin Exerts Cardioprotective Effects on Ischemia/Reperfusion Injury through the Modulation of mitoKATP Channels
title_sort erucin exerts cardioprotective effects on ischemia reperfusion injury through the modulation of mitokatp channels
topic erucin
isothiocyanates
mitochondrial channels
mitoK<sub>ATP</sub> channels
H<sub>2</sub>S
H<sub>2</sub>S donors
url https://www.mdpi.com/2227-9059/11/12/3281
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