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Resveratrol alters human endothelial cells redox state and causes mitochondrial-dependent cell death

Posadino, Anna Maria and Cossu, Annalisa and Giordo, Roberta and Zinellu, Angelo and Sotgia, Salvatore and Vardeu, Antonella and Thi Hoa, Phu and Van Nguyen, Le Hong and Carru, Ciriaco and Pintus, Gianfranco (2015) Resveratrol alters human endothelial cells redox state and causes mitochondrial-dependent cell death. Food and Chemical Toxicology, Vol. 78 , p. 10-16. ISSN 0278-6915. eISSN 1873-6351. Article.

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DOI: 10.1016/j.fct.2015.01.017

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.

Item Type:Article
ID Code:10687
Status:Published
Refereed:Yes
Uncontrolled Keywords:Antioxidants, resveratrol, endothelial cells, pro-oxidant effect, cell damage
Subjects:Area 05 - Scienze biologiche > BIO/10 Biochimica
Area 05 - Scienze biologiche > BIO/12 Biochimica clinica e biologia molecolare clinica
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Biomediche
Publisher:Elsevier
ISSN:0278-6915
eISSN:1873-6351
Deposited On:16 Feb 2015 10:16

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