title: The Citrus Flavanone Naringenin Produces Cardioprotective Effects in Hearts from 1 Year Old Rat, through Activation of mitoBK Channels.
abstract: Background and Purpose: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.Experimental Approach: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.Key Results:Naringenin protected the hearts of 1 year old rats in bothex vivoandin vivoI/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.Conclusion and Implications: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.
authors.affiliation: Department of Pharmacy, University of PisaPisa, Italy; Interdepartmental Research Center "Nutraceuticals and Food for Health"Pisa, Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Testai
authors.affiliation: Department of Pharmacy, University of PisaPisa, Italy; Interdepartmental Research Center "Nutraceuticals and Food for Health"Pisa, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Da Pozzo
authors.affiliation: Department of Pharmacy, University of Pisa Pisa, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Piano
authors.affiliation: Department of Pharmacy, University of PisaPisa, Italy; Interdepartmental Research Center "Nutraceuticals and Food for Health"Pisa, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Pistelli
authors.affiliation: Department of Pharmacy, University of Pisa Pisa, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gargini
authors.affiliation: Department of Pharmacy, University of Pisa Pisa, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Breschi
authors.affiliation: Department of Pharmacy, University of PisaPisa, Italy; Interdepartmental Research Center "Nutraceuticals and Food for Health"Pisa, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Braca
authors.affiliation: Department of Pharmacy, University of PisaPisa, Italy; Interdepartmental Research Center "Nutraceuticals and Food for Health"Pisa, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Martini
authors.affiliation: Department of Pharmacy, University of PisaPisa, Italy; Interdepartmental Research Center "Nutraceuticals and Food for Health"Pisa, Italy.
authors.forename: Alma
authors.initials: A
authors.lastname: Martelli
authors.affiliation: Department of Pharmacy, University of PisaPisa, Italy; Interdepartmental Research Center "Nutraceuticals and Food for Health"Pisa, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Calderone
keywords: cardioprotection; flavonoids; ischemia/reperfusion injury; mitochondrial potassium channels; naringenin; nutraceutics