Astaxanthin ameliorates cardiomyocyte apoptosis after coronary microembolization by inhibiting oxidative stress via Nrf2/HO-1 pathway in rats
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Coronary microembolization (CME) caused by physical obstruction in coronary microcirculation induces myocardial apoptosis and cardiac dysfunction, and it was reported that the inactivation of the Nrf2/HO-1 signaling was involved in this process. Astaxanthin (AST) is a reddish pigment that belongs to keto-carotenoids. It is also a potent antioxidant and has been reported to activate Nrf2/HO-1 signaling in vein endothelial cells. However, it is still unknown whether AST is able to activate Nrf2/HO-1 signaling pathway to protect cardiac functions from CME in vivo. To address this question, rats were orally administrated with AST or AST plus Zinc protoporphyrin IX (ZnPP, a HO-1 inhibitor), followed by CME modeling operation. Then, cardiac function was evaluated by echocardiographic measurement. Myocardial infarction was measured by HBFP staining, and apoptosis was assessed by TUNEL staining. The protein levels and mRNA expressions of Bax and Bcl-2 were measured by Western blot and qRT-PCR, respectively. ELISA was performed to measure the activity of enzymes related to oxidative stress. AST pretreatment dramatically attenuated CME-induced cardiac dysfunction, myocardial infarction, and cardiomyocyte apoptosis. Mechanistically, AST suppressed CME-induced oxidative stress by re-activating Nrf2/HO-1 signaling. HO-1 inhibitor ZnPP completely eliminated the benefits of AST in CEM, supporting the critical role of Nrf2/HO-1 signaling in mediating the cardioprotective function of AST in CME. Conclusion: AST suppresses oxidative stress via activating Nrf2/HO-1 pathway and thus prevents CME-induced cardiomyocyte apoptosis and ameliorates cardiac dysfunction in rats.
KeywordsCoronary microembolization Astaxanthin Oxidative stress Cardiomyocyte apoptosis Nrf2/HO-1 signaling
Yugang Xue, Chuang Sun, Qimeng Hao conducted the experiments and analyzed the data; Jin Cheng conceived and designed the research and wrote the manuscript. All the authors read and approved the manuscript.
Compliance with ethical standards
Conflicts of interest
The authors declare that they have no conflict of interest.
Research involving human participants and/or animals
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
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