Cardioprotective effects of dapsone against doxorubicin-induced cardiotoxicity in rats

• Published in: Cancer chemotherapy and pharmacology 2020-03, Vol.85 (3), p.563-571
• Main Authors: Sheibani, Mohammad, Nezamoleslami, Sadaf, Faghir-Ghanesefat, Hedyeh, Emami, Amir hossein, Dehpour, Ahmad Reza
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Antibiotics; Antioxidants; Antioxidants - metabolism; Apoptosis - drug effects; Cancer Research; Cardiotoxicity; Cardiotoxicity - drug therapy; Cardiotoxicity - metabolism; Cytokines - metabolism; Dapsone; Dapsone - pharmacology; Diaminodiphenylsulfone; Doxorubicin; Doxorubicin - adverse effects; EKG; Excitation; Free radicals; Heart - drug effects; Inflammation; Inflammation - chemically induced; Inflammation - metabolism; Leprosy; Levels; Male; Malondialdehyde; Malondialdehyde - metabolism; Medicine; Medicine & Public Health; Muscle contraction; Muscles; Muscular function; Myocardium - metabolism; Oncology; Original Article; Oxidants; Oxidative stress; Oxidative Stress - drug effects; Oxidizing agents; Pharmacology/Toxicology; Protective Agents - pharmacology; Rats; Rats, Wistar; Serum levels; Superoxide dismutase; Toxicity; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-019-04019-6

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.