Resveratrol alters human endothelial cells redox state and causes mitochondrial-dependent cell death.
Food Chem Toxicol
; 78: 10-6, 2015 Apr.
Article
em En
| MEDLINE
| ID: mdl-25656643
ABSTRACT
Studies analyzing the impact of natural antioxidants (NA) on Endothelial Cells (ECs) have dramatically increased during the last years, since a deregulated ECs redox state is at the base of the onset and progression of several cardiovascular diseases. However, whether NA can provide cardiovascular benefits is still a controversial area of debate. Resveratrol (RES), a natural polyphenol found in grapes, is believed to provide cardiovascular benefits by virtue of its antioxidant effect on the endothelium. Here, we report that tissue-attainable doses of resveratrol increased the intracellular oxidative state, thus affecting mitochondrial membrane depolarization and inducing EC death. Cyclosporine A, a mitochondrial permeability transition pore inhibitor, prevented oxidative-mediated cell death, thus implicating mitochondria in resveratrol-induced EC impairment. The specific cytochrome P450 (CYP) 2C9 inhibitor, sulfaphenazole, counteracted both oxidative stress and mitochondrial membrane depolarization, providing EC protection against resveratrol-elicited pro-oxidant effects. Our findings strongly suggest that CYP2C9 mediates resveratrol-induced oxidative stress leading to mitochondria impairment and EC death.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Estilbenos
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Estresse Oxidativo
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Membranas Mitocondriais
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Células Endoteliais da Veia Umbilical Humana
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Mitocôndrias
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article