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Cardioprotective Effects of Dapsone Against Doxorubicin-Induced Cardiotoxicity in Rats Publisher Pubmed



Sheibani M1, 2 ; Nezamoleslami S1, 2 ; Faghirghanesefat H1, 2 ; Emami A3 ; Dehpour AR1, 2
Authors
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Authors Affiliations
  1. 1. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran
  2. 2. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Hematology-Oncology Department, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran

Source: Cancer Chemotherapy and Pharmacology Published:2020


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. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.