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Resveratrol alters human endothelial cells redox state and causes mitochondrial-dependent cell death
- Source :
- Food and Chemical Toxicology. 78:10-16
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
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.
- Subjects :
- Programmed cell death
Cytochrome P-450 CYP2C9 Inhibitors
Cell Survival
Oxidative phosphorylation
Pharmacology
Mitochondrion
Resveratrol
Biology
Toxicology
medicine.disease_cause
Mitochondrial Membrane Transport Proteins
chemistry.chemical_compound
Sulfaphenazole
Stilbenes
Human Umbilical Vein Endothelial Cells
medicine
Humans
Cell damage
Cytochrome P-450 CYP2C9
Cell Death
Mitochondrial Permeability Transition Pore
food and beverages
General Medicine
medicine.disease
Mitochondria
Oxidative Stress
Biochemistry
Mitochondrial permeability transition pore
chemistry
Mitochondrial Membranes
Cyclosporine
Reactive Oxygen Species
Oxidative stress
Intracellular
Food Science
Subjects
Details
- ISSN :
- 02786915
- Volume :
- 78
- Database :
- OpenAIRE
- Journal :
- Food and Chemical Toxicology
- Accession number :
- edsair.doi.dedup.....18ae57883c0fc587fb81e90d23e6f25b