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Coenzyme Q10 Cardioprotective Effects Against Doxorubicin-Induced Cardiotoxicity in Wistar Rat

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Abstract

In the present study, we investigated the cardioprotective effects of coenzyme Q10 (Q10) against doxorubicin (DOXO) induced cardiomyopathy. Twenty adult rats were distributed in four experimental groups: group 1 received NaCl 0.9% at 1 ml/day for 14 days; group 2 received Q10 at 1 mg/kg/day for 14 days; group 3 received initial 7 days of treatment with NaCl 0.9% followed by a single dose of doxorubicin (12.5 mg/kg IP) and another 7 days of NaCl; and group 4 received initial 7 days of Q10 1 mg/kg/day, followed by a single dose of doxorubicin (12.5 mg/kg IP) and another 7 days of Q10. At the end of 14 days, systolic, diastolic and mean blood pressure, electrocardiogram (ECG), complete blood count, and serum biochemical profile were evaluated. We also analyzed heart histological and ultrastructure analysis, and estimated heart’s oxidative stress and lipid peroxidation. DOXO administration altered ECG, with increase heart rate, P-wave duration, PR interval duration, and T-wave amplitude. All the parameters were significantly reduced following Q10 treatment. DOXO also caused increase in CK, CK-MB, LDH, and urea levels, which were not mitigated by Q10 treatment. However, Q10 reduced oxidative stress by interfering with superoxide dismutase, significantly decreasing lipid peroxidation in heart tissue. DOXO administration also leads to several histological and ultrastructure alterations including cardiomyocyte degeneration and intense intracelullar autophagosomes, all minimized by Q10 treatment. Q10 treatment prevented the ECG changes, minimized oxidative stress, lipid peroxidation, and DOXO-induced heart tissue alterations. Our findings suggest that pre- and post-treatment with Q10 exerts potential cardioprotective effect against the DOX-induced cardiotoxicity.

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Acknowledgments

The authors would like to acknowledge the Center of Microscopy at the Universidade Federal de Minas Gerais (http://www.microscopia.ufmg.br) for providing the equipment and technical support for experiments involving electron microscopy.

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Authors and Affiliations

  1. Laboratório de Toxicologia Veterinária, Departamento de Medicina Veterinária, Escola de Veterinária e Zootecnia, Universidade Federal de Goiás, Goiânia, Brazil

    Ana Flávia M. Botelho

  2. Laboratório de Toxicologia Veterinária, Departamento de Clínica e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    Marthin R. Lempek, Stephanie Elise M. T. Branco, Marina M. Nogueira, Maria Elvira de Almeida, Aristóteles G. Costa, Thalita G. Freitas, Michele Caroline R. C. Rocha, Gleidice Lavalle & Marília M. Melo

  3. Laboratório de Patologia Veterinária, Departamento de Clínica e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    Matheus V. L. Moreira

  4. Laboratório de Membranas Excitáveis e Biologia Cardiovascular, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    Tatiane O. Barreto & Jader C. Santos

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  1. Ana Flávia M. Botelho
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Correspondence to Ana Flávia M. Botelho.

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The authors declare that there is no conflict of interests regarding the publication of this article.

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All experimental animals were used in accordance with experimentation ethics, respecting animal welfare and minimizing any discomfort. The present study was approved by the Ethics Committee of Animal Use (CEUA) of the Federal University of Minas Gerais, Protocol No 74/2017.

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Botelho, A.F.M., Lempek, M.R., Branco, S.E.M.T. et al. Coenzyme Q10 Cardioprotective Effects Against Doxorubicin-Induced Cardiotoxicity in Wistar Rat. Cardiovasc Toxicol 20, 222–234 (2020). https://doi.org/10.1007/s12012-019-09547-4

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