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Toxicol Appl Pharmacol ; 486: 116951, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38705401

RESUMEN

Cardiac lipotoxicity is a prevalent consequence of lipid metabolism disorders occurring in cardiomyocytes, which in turn precipitates the onset of heart failure. Mimetics of brain-derived neurotrophic factor (BDNF), such as 7,8-dihydroxyflavone (DHF) and 7,8,3'-trihydroxyflavone (THF), have demonstrated significant cardioprotective effects. However, it remains unclear whether these mimetics can protect cardiomyocytes against lipotoxicity. The aim of this study was to examine the impact of DHF and THF on the lipotoxic effects induced by palmitic acid (PA), as well as the concurrent mitochondrial dysfunction. H9c2 cells were subjected to treatment with PA alone or in conjunction with DHF or THF. Various factors such as cell viability, lactate dehydrogenase (LDH) release, death ratio, and mitochondrial function including mitochondrial membrane potential (MMP), mitochondrial-derived reactive oxygen species (mito-SOX) production, and mitochondrial respiration were assessed. PA dose-dependently reduced cell viability, which was restored by DHF or THF. Additionally, both DHF and THF decreased LDH content, death ratio, and mito-SOX production, while increasing MMP and regulating mitochondrial oxidative phosphorylation in cardiomyocytes. Moreover, DHF and THF specifically activated Akt signaling. The protective effects of DHF and THF were abolished when an Akt inhibitor was used. In conclusion, BDNF mimetics attenuate PA-induced injury in cardiomyocytes by alleviating mitochondrial impairments through the activation of Akt signaling.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Flavonas , Potencial de la Membrana Mitocondrial , Miocitos Cardíacos , Ácido Palmítico , Proteínas Proto-Oncogénicas c-akt , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Ácido Palmítico/toxicidad , Ácido Palmítico/farmacología , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Ratas , Línea Celular , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Flavonas/farmacología , Supervivencia Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/metabolismo , Especies Reactivas de Oxígeno/metabolismo
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