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Cardioprotective role of a magnolol and honokiol complex in the prevention of doxorubicin-mediated cardiotoxicity in adult rats

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Abstract

Doxorubicin (DOXO) induces marked cardiotoxicity, though increased oxidative stress while there are some documents related with cardioprotective effects of some antioxidants against organ-toxicity during cancer treatment. Although magnolia bark has some antioxidant-like effects, its action in DOXO-induced heart dysfunction has not be shown clearly. Therefore, here, we aimed to investigate the cardioprotective action of a magnolia bark extract with active component magnolol and honokiol complex (MAHOC; 100 mg/kg) in DOXO-treated rat hearts. One group of adult male Wistar rats was injected with DOXO (DOXO-group; a cumulative dose of 15 mg/kg in 2-week) or saline (CON-group). One group of DOXO-treated rats was administered with MAHOC before DOXO (Pre-MAHOC group; 2-week) while another group was administered with MAHOC following the 2-week DOXO (Post-MAHOC group). MAHOC administration, before or after DOXO, provided full survival of animals during 12–14 weeks, and significant recoveries in the systemic parameters of animals such as plasma levels of manganese and zinc, total oxidant and antioxidant statuses, and also systolic and diastolic blood pressures. This treatment also significantly improved heart function including recoveries in end-diastolic volume, left ventricular end-systolic volume, heart rate, cardiac output, and prolonged P-wave duration. Furthermore, the MAHOC administrations improved the structure of left ventricles such as recoveries in loss of myofibrils, degenerative nuclear changes, fragmentation of cardiomyocytes, and interstitial edema. Biochemical analysis in the heart tissues provided the important cardioprotective effect of MAHOC on the redox regulation of the heart, such as improvements in activities of glutathione peroxidase and glutathione reductase, and oxygen radical-absorbing capacity of the heart together with recoveries in other systemic parameters of animals, while all of these benefits were observed in the Pre-MAHOC treatment group, more prominently. Overall, one can point out the beneficial antioxidant effects of MAHOC in chronic heart diseases as a supporting and complementing agent to the conventional therapies.

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Funding

This work is supported by Lokman Hekim University Scientific Research Projects Coordination Unit. Project No.: 202AP404, 2022.

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Authors and Affiliations

  1. Department of Biophysics, Faculty of Medicine, Ankara University, Ankara, Turkey

    Irem Aktay, Yusuf Olgar, Aysegul Durak, Erkan Tuncay, Kamil Can Akcali & Belma Turan

  2. Stem Cell Institute, Ankara University, Ankara, Turkey

    Ceylan Verda Bitirim & Kamil Can Akcali

  3. Department of Histology and Embryology, Faculty of Medicine, Ankara University, Ankara, Turkey

    Deniz Billur

  4. Department of Biophysics, Faculty of Medicine, Lokman Hekim University, Ankara, Turkey

    Belma Turan

  5. Ankara University Stem cell Institute, Ankara, Turkey

    Ceylan Verda Bitirim

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  1. Irem Aktay
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Contributions

IA, CVB, YO, DB, and AD conducted all experiments. ET, CVB, YO, and DB analyzed the data. KCA contributed to the interpretation of the results. BT conceived, designed, and interpreted the data and wrote, edited, and approved the manuscript.

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Aktay, I., Bitirim, C.V., Olgar, Y. et al. Cardioprotective role of a magnolol and honokiol complex in the prevention of doxorubicin-mediated cardiotoxicity in adult rats. Mol Cell Biochem 479, 337–350 (2024). https://doi.org/10.1007/s11010-023-04728-w

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