AUTHOR=Testai Lara , Da Pozzo Eleonora , Piano Ilaria , Pistelli Luisa , Gargini Claudia , Breschi Maria Cristina , Braca Alessandra , Martini Claudia , Martelli Alma , Calderone Vincenzo 

TITLE=The Citrus Flavanone Naringenin Produces Cardioprotective Effects in Hearts from 1 Year Old Rat, through Activation of mitoBK Channels

JOURNAL=Frontiers in Pharmacology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00071

DOI=10.3389/fphar.2017.00071

ISSN=1663-9812

ABSTRACT=<p><bold>Background and Purpose:</bold> Incidence of cardiovascular disorders increases with age, because of a dramatic fall of endogenous self-defense mechanisms and increased vulnerability of myocardium. Conversely, the effectiveness of many cardioprotective drugs is blunted in hearts of 1 year old rat. The Citrus flavanone naringenin (NAR) was reported to promote cardioprotective effects against ischemia/reperfusion (I/R) injury, through the activation of mitochondrial large conductance calcium-activated potassium channel (mitoBK). These effects were observed in young adult rats, but no data are available about the possible cardioprotective effects of NAR in aged animals.</p><p><bold>Experimental Approach:</bold> This study aimed at evaluating the potential cardioprotective effects of NAR against I/R damage in 1 year old rats, and the possible involvement of mitoBK.</p><p><bold>Key Results:</bold> Naringenin protected the hearts of 1 year old rats in both <italic>ex vivo</italic> and <italic>in vivo</italic> I/R protocols. Noteworthy, these effects were antagonized by paxilline, a selective BK-blocker. The cardioprotective effects of NAR were also observed in senescent H9c2 cardiomyoblasts. In isolated mitochondria from hearts of 1 year old, NAR exhibited the typical profile of a mitoBK opener. Finally, Western Blot analysis confirmed a significant (albeit reduced) presence of BK-forming alpha and beta subunits, both in cardiac tissue of 1 year old rats and in senescent H9c2 cells.</p><p><bold>Conclusion and Implications:</bold> This is the first work reporting cardioprotective effects of NAR in 1 year old rats. Although further studies are needed to better understand the whole pathway involved in the NAR-mediated cardioprotection, these preliminary data represent a promising perspective for a rational nutraceutical use of NAR in aging.</p>