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

Jing-Yi Sun,Xiao-Yan Fu,Yuan Li,Xiao-Ting Fu,Ming-Feng Yang,Cun-Dong Fan,Bao-Liang Sun,Ya-Jun Hou

doi:10.3389/fphys.2017.01041

Abstract

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.

Highlights

Cardiovascular diseases (CVD) as the leading causes of death globally represent one of the most challenges in clinic (Lee et al, 2016)
The protective effects and mechanism of ATX against Hcy-induced cardiotoxicity in H9c2 rat cardiomyocytes and an experimental animal model were evaluated, and the results indicated that ATX attenuated Hcy-induced cardiotoxicity in vitro and in vivo by inhibiting mitochondrial dysfunction and oxidative damage, which validated its potential application in chemoprevention and chemotherapy of human cardiovascular diseases (CVD)
In the present study, Hcy-induced cardiotoxicity and underlying mechanism were evaluated in H9c2 rat cardiomyocytes and Hcyinjured animal model, which are both accepted as good models for exploring the cardiotoxicity in vitro and in vivo

Summary

Introduction

Cardiovascular diseases (CVD) as the leading causes of death globally represent one of the most challenges in clinic (Lee et al, 2016). Endothelial cells play key role in vascular homeostasis, and endothelial dysfunction contributed to the development of human CVD (Zhang et al, 2001; Ungvari et al, 2003; Austin et al, 2004). Homocysteine (Hcy) is an intermediate metabolite of Astaxanthin Inhibits Homocysteine-Induced Cardiotoxicity cysteine and methionine. Large numbers of evidences have confirmed that elevated plasma levels of Hcy as an independent risk factor may induce endothelial dysfunction through oxidative stress and apoptosis, and eventually lead to the occurrence and development of human CVD (Almashhadany et al, 2015; Baggott and Tamura, 2015). Hcy-mediated toxicity toward cardiomyocytes was not well demonstrated, and the underlying mechanism remains elusive. H9c2 rat cardiomyocytes and an Hcy-injured experimental animal model were employed to evaluate the potential cardiotoxicity and the underlying mechanism

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Results

Conclusion