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.
Resveratrol alters human endothelial cells redox state and causes mitochondrial-dependent cell death / Posadino, Am; Cossu, A; Giordo, R; Zinellu, Angelo; Sotgia, S; Vardeu, A; Hoa, Pt; Nguyen, Lhv; Carru, Ciriaco; Pintus, Gianfranco. - In: FOOD AND CHEMICAL TOXICOLOGY. - ISSN 1873-6351. - 78:(2015), pp. 78C:10-16.10-78C:10-16.16. [10.1016/j.fct.2015.01.017]