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Cardioprotective effects of dapsone against doxorubicin-induced cardiotoxicity in rats

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Abstract

Purpose

It has been supposed that cardiac toxicity of doxorubicin is due to its production of free radicals and inflammatory cytokines. Dapsone, an antibiotic drug which is the principal in a multidrug regimen for the treatment of leprosy, is a sulfone with anti-inflammatory and antioxidant immunosuppressive properties. Therefore, we designed this study to investigate the possible effects of dapsone on doxorubicin-induced cardiotoxicity.

Methods

Male rats were administrated doxorubicin (2.5 mg/kg) and dapsone (1, 3, 10 mg/kg) intraperitoneally six times in 2 weeks. Then electrocardiographic (ECG) parameters (QRS complexes, RR and QT intervals) alternation, papillary muscle contraction and excitation, and histopathological changes were assessed. Also, the heart tissue levels of malondialdehyde (MDA) as oxidant factor and superoxide dismutase (SOD) as antioxidant enzyme, tumor necrosis factor-alpha (TNF-α) and serum level of CK-MB were analyzed.

Results

Administration of dapsone with doxorubicin significantly reversed alterations induced by doxorubicin in serum levels of CK-MB, ECG parameters, papillary muscle contractility and excitation. Furthermore, the measurement of MDA, SOD and TNF-α tissue level indicated that dapsone significantly reduced oxidative stress and inflammation. These findings were consistent with histopathological analysis.

Conclusion

Dapsone exerts cardioprotective effects on doxorubicin-induced cardiotoxicity through its anti-inflammatory and antioxidant mechanism.

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Acknowledgements

We deeply appreciate Gilaranco Co. for preparing dapsone powder for our experimental investigation.

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Author notes

  1. Mohammad Sheibani and Sadaf Nezamoleslami are considered as the first author of the manuscript.

Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran

    Mohammad Sheibani, Sadaf Nezamoleslami, Hedyeh Faghir-Ghanesefat & Ahmad Reza Dehpour

  2. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Sheibani, Sadaf Nezamoleslami, Hedyeh Faghir-Ghanesefat & Ahmad Reza Dehpour

  3. Hematology-Oncology Department, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Amir hossein Emami

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  1. Mohammad Sheibani
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Correspondence to Ahmad Reza Dehpour.

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The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The Ethical Committee of Tehran University of Medical Sciences approved all the in vivo work (IR.TUMS.MEDICINE.REC.1398.364) and they were in accordance with the National Institute of Health (NIH) Guidelines for the Care and Use of Laboratory Animals (HHS publication 85–23, 1985), legislation for the protection of animals used for scientific purposes (Directive 2010/63/EU).

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Sheibani, M., Nezamoleslami, S., Faghir-Ghanesefat, H. et al. Cardioprotective effects of dapsone against doxorubicin-induced cardiotoxicity in rats. Cancer Chemother Pharmacol 85, 563–571 (2020). https://doi.org/10.1007/s00280-019-04019-6

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