| It is well known that reactive oxygen species (ROS) and electrophiles are critically involved in the pathogenesis of cardiovascular diseases, such as atherosclerosis, ischemia-reperfusion injury, and drug-induced cardiomyopathy. Induction of endogenous antioxidants by chemicals represents a novel approach to exerting protective effects on ROS and electrophiles-mediated cardiovascular injury. In the current study, using rat aortic smooth muscle A10 cells and rat cardiomyocyte H9C2 cells as the in vitro systems, we have characterized the induction of cellular antioxidants by chemicals inducer, 3H-1,2-dithiole-3-thione (D3T), and determined the cytoprotection of such chemically-elevated endogenous antioxidative defenses against oxidative and electrophilic cardiovascular cell injury. Incubation of cardiovascular cells with D3T results in a remarkable induction of a battery of cellular antioxidants, including glutathione, glutathione peroxidase, GSSG reductase (GR), glutathione S-transferase (GST), catalase, and/or NAD(P)H:quinone-oxidoresuctase1(NQO1) and superoxide dismutase (SOD). Moreover, pretreatment of cardiovascular cells with D3T exhibited a marked protection against oxidative and electrophilic insults such as xanthine oxidase/xanthine-derived ROS, peroxynitrite, acrolein, 4-hydroxynonenal and/or cadmium, as determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT) reduction assay and morphological changes. In addition, C57BL/6 mice were used as an in vivo model to investigate the inducibility of endogenous antioxidants in cardiovascular tissues upon D3T administration. It was shown that administration with D3T increased GST, NQO1, catalase, GR, and SOD in cardiac tissue in C57BL/6 mice. Taken together, this study demonstrates that a number of endogenous antioxidants in cardiovascular cells/tissues can be induced by exposure to chemical inducer, D3T and such chemical induction of cellular antioxidants is accompanied by a significantly increased resistance to oxidative and electrophilic cardiovascular injury in vitro. Therefore, this study might have important implications in cardiovascular disorders. |
