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Doxorubicin‑induced cardiomyopathy is mitigated by empagliflozin via the modulation of endoplasmic reticulum stress pathways

  • Authors:
    • Akshi Malik
    • Ashim K. Bagchi
    • Davinder S. Jassal
    • Pawan K. Singal
  • View Affiliations / Copyright

    Affiliations: Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg R2H 2A6, Canada, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Copyright: © Malik et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 74
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    Published online on: March 12, 2024
       https://doi.org/10.3892/mmr.2024.13198
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Abstract

Doxorubicin (Dox) exhibits a high efficacy in the treatment of numerous types of cancer. However, the beneficial cytotoxic effects of Dox are often accompanied by an increase in the risk of cardiotoxicity. Oxidative stress (OS) plays a key role in Dox‑induced cardiomyopathy (DIC). OS in cardiomyocytes disrupts endoplasmic reticulum (ER) function, leading to the accumulation of misfolded/unfolded proteins known as ER stress. ER stress acts as an adaptive mechanism; however, prolonged ER stress together with OS may lead to the initiation of cardiomyocyte apoptosis. The present study aimed to explore the potential of an anti‑diabetic drug, empagliflozin (EMPA), in mitigating Dox‑induced ER stress and cardiomyocyte apoptosis. In the present study, the effects of 1 h pretreatment of EMPA on Dox‑treated cardiomyocytes isolated from Sprague‑Dawley rats were investigated. After 24 h, EMPA pre‑treatment promoted cell survival in the EMPA + Dox group compared with the Dox group. Results of the present study also demonstrated that EMPA mitigated overall ER stress, as the increased expression of ER stress markers was reduced in the EMPA + Dox group. Additionally, OS, inflammation and expression of ER stress apoptotic proteins were also significantly reduced following EMPA pre‑treatment in the EMPA + Dox group. Thus, EMPA may exert beneficial effects on Dox‑induced ER stress and may exhibit potential changes that can be utilised to further evaluate the role of EMPA in mitigating DIC.
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Copy and paste a formatted citation
Spandidos Publications style
Malik A, Bagchi AK, Jassal DS and Singal PK: Doxorubicin‑induced cardiomyopathy is mitigated by empagliflozin via the modulation of endoplasmic reticulum stress pathways. Mol Med Rep 29: 74, 2024.
APA
Malik, A., Bagchi, A.K., Jassal, D.S., & Singal, P.K. (2024). Doxorubicin‑induced cardiomyopathy is mitigated by empagliflozin via the modulation of endoplasmic reticulum stress pathways. Molecular Medicine Reports, 29, 74. https://doi.org/10.3892/mmr.2024.13198
MLA
Malik, A., Bagchi, A. K., Jassal, D. S., Singal, P. K."Doxorubicin‑induced cardiomyopathy is mitigated by empagliflozin via the modulation of endoplasmic reticulum stress pathways". Molecular Medicine Reports 29.5 (2024): 74.
Chicago
Malik, A., Bagchi, A. K., Jassal, D. S., Singal, P. K."Doxorubicin‑induced cardiomyopathy is mitigated by empagliflozin via the modulation of endoplasmic reticulum stress pathways". Molecular Medicine Reports 29, no. 5 (2024): 74. https://doi.org/10.3892/mmr.2024.13198
Copy and paste a formatted citation
x
Spandidos Publications style
Malik A, Bagchi AK, Jassal DS and Singal PK: Doxorubicin‑induced cardiomyopathy is mitigated by empagliflozin via the modulation of endoplasmic reticulum stress pathways. Mol Med Rep 29: 74, 2024.
APA
Malik, A., Bagchi, A.K., Jassal, D.S., & Singal, P.K. (2024). Doxorubicin‑induced cardiomyopathy is mitigated by empagliflozin via the modulation of endoplasmic reticulum stress pathways. Molecular Medicine Reports, 29, 74. https://doi.org/10.3892/mmr.2024.13198
MLA
Malik, A., Bagchi, A. K., Jassal, D. S., Singal, P. K."Doxorubicin‑induced cardiomyopathy is mitigated by empagliflozin via the modulation of endoplasmic reticulum stress pathways". Molecular Medicine Reports 29.5 (2024): 74.
Chicago
Malik, A., Bagchi, A. K., Jassal, D. S., Singal, P. K."Doxorubicin‑induced cardiomyopathy is mitigated by empagliflozin via the modulation of endoplasmic reticulum stress pathways". Molecular Medicine Reports 29, no. 5 (2024): 74. https://doi.org/10.3892/mmr.2024.13198
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