title: Dehydrosilybin attenuates the production of ROS in rat cardiomyocyte mitochondria with an uncoupler-like mechanism.
abstract: Reactive oxygen species (ROS) originating from mitochondria are perceived as a factor contributing to cell aging and means have been sought to attenuate ROS formation with the aim of extending the cell lifespan. Silybin and dehydrosilybin, two polyphenolic compounds, display a plethora of biological effects generally ascribed to their known antioxidant capacity. When investigating the cytoprotective effects of these two compounds in the primary cell cultures of neonatal rat cardiomyocytes, we noted the ability of dehydrosilybin to de-energize the cells by monitoring JC-1 fluorescence. Experiments evaluating oxygen consumption and membrane potential revealed that dehydrosilybin uncouples the respiration of isolated rat heart mitochondria albeit with a much lower potency than synthetic uncouplers. Furthermore, dehydrosilybin revealed a very high potency in suppressing ROS formation in isolated rat heart mitochondria with IC(50) = 0.15 μM. It is far more effective than its effect in a purely chemical system generating superoxide or in cells capable of oxidative burst, where the IC(50) for dehydrosilybin exceeds 50 μM. Dehydrosilybin also attenuated ROS formation caused by rotenone in the primary cultures of neonatal rat cardiomyocytes. We infer that the apparent uncoupler-like activity of dehydrosilybin is the basis of its ROS modulation effect in neonatal rat cardiomyocytes and leads us to propose a hypothesis on natural ischemia preconditioning by dietary polyphenols.
authors.affiliation: Institute of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Gabrielová
authors.forename: Martin
authors.initials: M
authors.lastname: Jabůrek
authors.forename: Radek
authors.initials: R
authors.lastname: Gažák
authors.forename: Jitka
authors.initials: J
authors.lastname: Vostálová
authors.forename: Jan
authors.initials: J
authors.lastname: Ježek
authors.forename: Vladimír
authors.initials: V
authors.lastname: Křen
authors.forename: Martin
authors.initials: M
authors.lastname: Modrianský
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001562:Benzimidazoles; D002232:Carbocyanines; D005456:Fluorescent Dyes; D020128:Inhibitory Concentration 50; D008928:Mitochondria / Q000378:metabolism*; D015394:Molecular Structure; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012402:Rotenone / Q000633:toxicity; D012838:Silymarin / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001562:Benzimidazoles; D002232:Carbocyanines; D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; D012838:Silymarin; C515097:dehydrosilybin; D012402:Rotenone; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine