Tehran University of Medical Sciences Acta Medica Iranica 0044-6025 59 7 2021 08 25 406 415 Mohammad Sheibani Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Hedyeh Faghir-Ghanesefat Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. AND Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Yaser Azizi Physiology Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.AND Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Tahmineh Mokhtari CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China. AND Department of Psychology, University of Chinese Academy of Sciences, Beijing, China Hasan Yousefi‐Manesh Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. AND Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Roya Sattarzadeh Badkoubeh Department of Cardiology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran Amir Hossein Emami Department of Hematology-Oncology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran Ahmad Reza Dehpour Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. AND Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 2021 06 14 2021 06 26 The clinical use of doxorubicin as a potent chemotherapeutic agent is limited due to its dose-dependent cardiotoxicity. Oxidative stress and inflammatory pathways have a pivotal role in doxorubicin-induced cardiotoxicity. Sumatriptan, a 5-hydroxytryptamine (5-HT)1B/1D agonist that is mainly used to relieve migraine pain, has suggested exerting protective effects in numerous pathological conditions through antiinflammatory properties. The aim of the present study was to investigate the effects of sumatriptan on doxorubicin-induced cardiotoxicity and the contribution of anti-inflammation and antioxidative responses. Cardiotoxicity was induced by the administration of doxorubicin three times a week (2.5 mg/kg i.p) for two consecutive weeks on male rats. The animals were divided into four groups, including Control, Sumatriptan (0.1 mg/kg) received group, doxorubicin received group, and Doxorubicin+Sumatriptan (0.1 mg/kg) received group. Sumatriptan was administered 30 min before every injection of doxorubicin. On the last day of the second week, the body weight, mortality rate, electrocardiogram (ECG) and histopathological changes, cardiac inotropic study, and biochemical factors were evaluated. The loss of body weight, mortality rate, ECG parameters, reduction of papillary muscle contractility force as well as histopathological scores following administration of doxorubicin indicated severe cardiac damage. However, treatment with sumatriptan inhibited the functional and structural impairment induced by doxorubicin. In addition, sumatriptan could significantly reduce cardiac tissue levels of malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α), which were increased in the doxorubicin-treated rats. This study illustrated the protective effects of sumatriptan on decreasing doxorubicin-induced cardiac toxicity and mortality rate in part through inhibition of inflammatory and oxidative stress pathways. https://acta.tums.ac.ir/index.php/acta/article/view/9461