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RETRACTED ARTICLE: Alpha-Lipoic Acid Protects Against Doxorubicin-Induced Cardiotoxicity by Regulating Pyruvate Dehydrogenase Kinase 4

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This article was retracted on 03 April 2023

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Abstract

As a widely used anti-tumor anthracycline, the accumulation of Doxorubicin (DOX) in body causes irreparable cardiomyocyte damage and therefore is limited in clinical application. Strategies to prevent from DOX-associated cardiotoxicity are urgent for patients who undergo DOX-based chemotherapy. Since oxidative stress injury being the major reason for myocardial toxicity of DOX, here we demonstrated that, Alpha-lipoic acid (ALA), which is a reductive agent, plays a cardioprotective role in attenuating DOX-induced cardiotoxicity by inhibiting pyruvate dehydrogenase kinase 4 (PDK4) expression. In vivo, the beneficial effect of ALA was evidenced by increased survival rate, mechanical contraction, and oxidative phosphorylation, while decreased reactive oxidative species (ROS) and apoptosis. In vitro, PDK4 overexpression remarkably increased DOX-induced apoptosis and ROS production in H9C2 cells. Notably, the protective effect of ALA was abrogated by PDK4 overexpression. We further used PDK4 knockout mice to identify the role of PDK4 in DOX-induced cardiotoxicity. Results elicited that PDK4 deficiency showed a consistent effect in protecting DOX cardiotoxicity as ALA treatment, which was evidenced by restored redox homeostasis and mitochondrial metabolism, finally inhibited myocardial injury. In conclusion, the cardioprotective role of ALA against DOX cardiotoxicity was dependent on PDK4-mediated regulation of oxidative stress and mitochondria metabolism.

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Data Availability

The datasets generated and used during current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank the support of Zhejiang Provincial Research Projects of Medical and Healthy Industries (grant nos. 2020KY424 and 2021KY485).

Funding

This work was supported by Zhejiang Provincial Research Projects of Medical and Healthy Industries (grant nos. 2020KY424 and 2021KY485).

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Author notes

  1. Fangxiao Gong and Jun Jin contributed equally to this work.

Authors and Affiliations

  1. Emergency and Critical Care Center, Intensive Care Unit, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China

    Fangxiao Gong & Jun Jin

  2. Emergency and Critical Care Center, Department of Emergency Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China

    Hengjie Li

  3. Center for Rehabilitation Medicine, Department of Anesthesiology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Gongshu District, Hangzhou, 310014, Zhejiang, China

    Hui Mao

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Contributions

FG and JJ performed the formal analysis and wrote the original draft. HL supervised the study and validated the data. HM reviewed and edited the manuscript. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Hui Mao.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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The study was approved by the Institutional Animal Care and Use Committee (IACUC) of Hangzhou Medical College (Reference no: HMC.NO.2020-98).

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This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.1007/s12012-023-09791-9"

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Gong, F., Jin, J., Li, H. et al. RETRACTED ARTICLE: Alpha-Lipoic Acid Protects Against Doxorubicin-Induced Cardiotoxicity by Regulating Pyruvate Dehydrogenase Kinase 4. Cardiovasc Toxicol 22, 879–891 (2022). https://doi.org/10.1007/s12012-022-09766-2

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