Astaxanthin Attenuates Homocysteine-Induced Cardiotoxicity in Vitro and in Vivo by Inhibiting Mitochondrial Dysfunction and Oxidative Damage
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...
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Frontiers Media S.A.
2017-12-01
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| Series: | Frontiers in Physiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphys.2017.01041/full |
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| author | Cun-dong Fan Jing-yi Sun Xiao-ting Fu Ya-jun Hou Yuan Li Ming-feng Yang Xiao-yan Fu Bao-liang Sun Bao-liang Sun |
| author_facet | Cun-dong Fan Jing-yi Sun Xiao-ting Fu Ya-jun Hou Yuan Li Ming-feng Yang Xiao-yan Fu Bao-liang Sun Bao-liang Sun |
| author_sort | Cun-dong Fan |
| collection | DOAJ |
| description | 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 in vivo 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 in vitro and in vivo 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. |
| first_indexed | 2024-12-24T04:26:47Z |
| format | Article |
| id | doaj.art-a75a2004fb8f46abad7834ea134161e7 |
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| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-24T04:26:47Z |
| publishDate | 2017-12-01 |
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| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-a75a2004fb8f46abad7834ea134161e72022-12-21T17:15:33ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2017-12-01810.3389/fphys.2017.01041301316Astaxanthin Attenuates Homocysteine-Induced Cardiotoxicity in Vitro and in Vivo by Inhibiting Mitochondrial Dysfunction and Oxidative DamageCun-dong Fan0Jing-yi Sun1Xiao-ting Fu2Ya-jun Hou3Yuan Li4Ming-feng Yang5Xiao-yan Fu6Bao-liang Sun7Bao-liang Sun8Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, ChinaWonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, South KoreaKey Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, ChinaKey Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, ChinaKey Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, ChinaKey Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, ChinaKey Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, ChinaKey Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, ChinaDepartment of Neurology, Affiliated Hospital of Taishan Medical University, Taian, ChinaHomocysteine (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 in vivo 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 in vitro and in vivo 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.http://journal.frontiersin.org/article/10.3389/fphys.2017.01041/fullhomocysteineastaxanthincardiovascular diseasesmitochondrial dysfunctionoxidative damage |
| spellingShingle | Cun-dong Fan Jing-yi Sun Xiao-ting Fu Ya-jun Hou Yuan Li Ming-feng Yang Xiao-yan Fu Bao-liang Sun Bao-liang Sun Astaxanthin Attenuates Homocysteine-Induced Cardiotoxicity in Vitro and in Vivo by Inhibiting Mitochondrial Dysfunction and Oxidative Damage Frontiers in Physiology homocysteine astaxanthin cardiovascular diseases mitochondrial dysfunction oxidative damage |
| title | Astaxanthin Attenuates Homocysteine-Induced Cardiotoxicity in Vitro and in Vivo by Inhibiting Mitochondrial Dysfunction and Oxidative Damage |
| title_full | Astaxanthin Attenuates Homocysteine-Induced Cardiotoxicity in Vitro and in Vivo by Inhibiting Mitochondrial Dysfunction and Oxidative Damage |
| title_fullStr | Astaxanthin Attenuates Homocysteine-Induced Cardiotoxicity in Vitro and in Vivo by Inhibiting Mitochondrial Dysfunction and Oxidative Damage |
| title_full_unstemmed | Astaxanthin Attenuates Homocysteine-Induced Cardiotoxicity in Vitro and in Vivo by Inhibiting Mitochondrial Dysfunction and Oxidative Damage |
| title_short | Astaxanthin Attenuates Homocysteine-Induced Cardiotoxicity in Vitro and in Vivo by Inhibiting Mitochondrial Dysfunction and Oxidative Damage |
| title_sort | astaxanthin attenuates homocysteine induced cardiotoxicity in vitro and in vivo by inhibiting mitochondrial dysfunction and oxidative damage |
| topic | homocysteine astaxanthin cardiovascular diseases mitochondrial dysfunction oxidative damage |
| url | http://journal.frontiersin.org/article/10.3389/fphys.2017.01041/full |
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