Estudios científicos

Resveratrol prevents doxorubicin cardiotoxicity through mitochondrial stabilization and the Sirt1 pathway

Abstract:

Doxorubicin (DOX) is one of the most effective chemotherapeutic drugs; however, its incidence of cardiotoxicity compromises its therapeutic index. DOX-induced heart failure is thought to be caused by reduction/oxidation cycling of DOX to generate oxidative stress and cardiomyocyte cell death. Resveratrol (RV), a stilbene found in red wine, has been reported to play a cardioprotective role in diseases associated with oxidative stress. The objective of this study was to test the ability of RV to protect against DOX-induced cardiomyocyte death. We hypothesized that RV protects cardiomyocytes from DOX-induced oxidative stress and subsequent cell death through changes in mitochondrial function. DOX induced a rapid increase in reactive oxygen species (ROS) production in cardiac cell mitochondria, which was inhibited by pretreatment with RV, most likely owing to an increase in MnSOD activity. This effect of RV caused additional polarization of the mitochondria in the absence and presence of DOX to increase mitochondrial function. RV pretreatment also prevented DOX-induced cardiomyocyte death. The protective ability of RV against DOX was abolished when Sirt1 was inhibited by nicotinamide. Our data suggest that RV protects against DOX-induced oxidative stress through changes in mitochondrial function, specifically the Sirt1 pathway leading to cardiac cell survival.

Comentarios divulgativos:

La doxorbicina (DOX) es uno de las drogas más efectivas en el tratamiento quimioterapeútico, sin embargo presenta cardiotoxicidad lo que compromete su utilidad terapeútica. DOX induce fallo cardiaco debido a que genera estes oxidativo y la muerte celular de los cardiomiocitos. El resveratrol, un estilbeno presente en el vino tinto se ha demostrado que juega un papel cardioprotector en las enfermedades asocadas a estres oxidativo. El objetivo de este estudio es testar la habilidad del resveratrol en la protección contra la muerte celular de los cardiomiocitos inducida por DOX. Los investigadores lanzan la hipótesis de que el resveratrol protege los cardiomiocitos del daño oxidativo producido por DOX el cual aumenta las especies resctivas del oxigeno (ROS). Los resultados sugieren que el resveratrol protege contra el estes oxidativo producido por DOX debido a cambios en la función mitocondrial, más específicamente en la ruta de Sirt-1