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

Abstract

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.

Erucin, a natural isothiocyanate, exerts pro‐angiogenic properties in cultured endothelial cells and reverts angiogenic impairment induced by high glucose

“…Previously, we described the antiinflammatory properties of ERU, as well as its promising protective effects against HG-induced vascular inflammation. (Ciccone, Piragine, et al, 2022a;Flori et al, 2023) Here we show that ERU, used at nanomolar concentrations (between 3 and 30 nM), induces functional endothelial migration through paxillin membrane mobilization and activation of multiple intracellular signalings. To date, this study represents one of the pioneering investigations on the effects of ERU at exceptionally low concentrations, considering that existing literature predominantly reports data within the 10-300 μM range.…”

“…ERU was produced from glucoerucin isolated from Eruca sativa Mill. defatted seed meals according to Flori et al (Flori et al, 2023). Briefly, pressure defatted seed meals (Bracco Company model Elle.Gi type 0.90) were added to boiling 70% ethanol, and homogenized at 7.600 rpm speed for 15 min.…”

Redox Regulation of Mitochondrial Potassium Channels Activity

“…In order to properly fulfill their task at physiological conditions, adequately react during stress conditions and finally adapt to a constantly changing environment, proteins including ion channels continually undergo modifications, which alter their properties and functions. Both mitoBK Ca and mitoK ATP may be upregulated due to S-sulfhydration by H 2 S [85][86][87].…”