Astaxanthin Attenuates Homocysteine-Induced Cardiotoxicity in Vitro and in Vivo by Inhibiting Mitochondrial Dysfunction and Oxidative Damage

• Published in: Frontiers in physiology Vol. 8; p. 1041
• Main Authors: Fan, Cun-Dong, Sun, Jing-Yi, Fu, Xiao-Ting, Hou, Ya-Jun, Li, Yuan, Yang, Ming-Feng, Fu, Xiao-Yan, Sun, Bao-Liang
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 12.12.2017
• Subjects: astaxanthin; cardiovascular diseases; homocysteine; mitochondrial dysfunction; oxidative damage; Physiology; homocysteine; oxidative damage; mitochondrial dysfunction; cardiovascular diseases; astaxanthin
• ISSN: 1664-042X; 1664-042X
• DOI: 10.3389/fphys.2017.01041

Homocysteine (Hcy) as an independent risk factor contributes to the occurrence and development of human cardiovascular diseases (CVD). Induction of oxidative stress and apoptosis was commonly accepted as the major mechanism in Hcy-induced cardiotoxicity. Astaxanthin (ATX) as one of the most powerful antioxidants exhibits novel cardioprotective potential against Hcy-induced endothelial dysfunction. However, the protective effect and mechanism of ATX against Hcy-induced cardiotoxicity in cardiomyocytes have not been elucidated yet. Herein, H9c2 rat cardiomyocytes and Hcy-injured animal model were employed in the present study. The MTT, flow cytometry analysis (FCM), TUNEL-DAPI and western blotting results all demonstrated that ATX significantly alleviated Hcy-induced cytotoxicity in H9c2 cells through inhibition of mitochondria-mediated apoptosis. The JC-1 and Mito-tracker staining both revealed that ATX pre-treatment blocked Hcy-induced mitochondrial dysfunction by regulating Bcl-2 family expression. Moreover, DCFH-DA and Mito-SOX staining showed that ATX effectively attenuated Hcy-induced oxidative damage via scavenging intracellular reactive oxygen species (ROS). Importantly, the ELISA and immunohistochemical results indicated that Hcy-induced cardiotoxicity was also significantly inhibited by ATX through inhibition of oxidative damage and apoptosis, and improvement of the angiogenesis. Taken together, our results demonstrated that ATX suppressed Hcy-induced cardiotoxicity and by inhibiting mitochondrial dysfunction and oxidative damage. Our findings validated the strategy of using ATX may be a highly efficient way to combat Hcy-mediated human CVD.