Posadino, Anna Maria and Cossu, Annalisa and Giordo, Roberta and Zinellu, Angelo and Sotgia, Salvatore and Vardeu, Antonella and Hoa, Phu Thi and Deiana, Luca and Carru, Ciriaco and Pintus, Gianfranco (2013) Coumaric acid induces mitochondrial damage and oxidative-mediated cell death of human endothelial cells. Cardiovascular toxicology, Vol. 13 (3), p. 301-306. eISSN 1559-0259. Article.
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Evidence that higher natural antioxidants (NA) intake provides cardiovascular protection is contradictory. The endothelium plays a pivotal role in cardiovascular homeostasis, and for this reason, the molecular events resulting from the interaction of NA with endothelial cells (ECs) are actively investigated. Here, we show that moderately high doses of coumaric acid (CA) induced intracellular reactive oxygen species (ROS) production, mitochondrial membrane depolarization and ECs death. Treatment of ECs with cyclosporine A, a mitochondrial permeability transition pore inhibitor, prevented the oxidative-mediated cell damage indicating mitochondrial involvement in CA-induced ECs impairment. CA-induced intracellular ROS generation was counteracted by the specific cytochrome P450 (CYP) 2C9 inhibitor sulfaphenazole (SPZ). SPZ also prevented CA-induced mitochondrial membrane depolarization and ECs death, implicating CYP2C9 in mediating the cellular response upon CA treatment. Our results indicate that moderately high doses of CA can promote CYP2C9-mediated oxidative stress eliciting mitochondrial-dependent ECs death and may pave the way toward mechanistic insight into NA effects on cardiovascular cells.
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