The activation of mitochondrial BK potassium channels contributes to the protective effects of naringenin against myocardial ischemia/reperfusion injury.
Biochem Pharmacol
; 85(11): 1634-43, 2013 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-23567997
ABSTRACT
Naringenin (NAR), flavonoid abundant in the genus Citrus, has been reported to interact with the large-conductance calcium-activated potassium channels (BK). Since activators of BK channels expressed in cardiac mitochondria trigger protective effects in several models of myocardial ischemia/reperfusion (I/R), this work aimed to evaluate the potential cardioprotective effects of NAR and the involvement of mitochondrial BK channels. In an in vivo model of acute infarct in rats, NAR (100mg/kg i.p.) significantly reduced the heart injury induced by I/R. This effect was antagonized by the selective BK-blocker paxilline (PAX). The cardioprotective dose of NAR did not cause significant effects on the blood pressure. In Largendorff-perfused rat hearts submitted to ischemia/reperfusion, NAR improved the post-ischemic functional parameters (left ventricle developed pressure and dP/dt) with lower extension of myocardial injury. On isolated rat cardiac mitochondria, NAR caused a concentration-dependent depolarization of mitochondrial membrane and caused a trans-membrane flow of thallium (potassium-mimetic cation). Both these effects were antagonized by selective blockers of BK channels. Furthermore, NAR half-reduced the calcium accumulation into the matrix of cardiac mitochondria exposed to high calcium concentrations. In conclusion, NAR exerts anti-ischemic effects through a "pharmacological preconditioning" that it is likely to be mediated, at least in part, by the activation of mitochondrial BK channels.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cardiotónicos
/
Daño por Reperfusión Miocárdica
/
Flavanonas
/
Canales de Potasio de Gran Conductancia Activados por el Calcio
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biochem Pharmacol
Año:
2013
Tipo del documento:
Article
País de afiliación:
Italia