Anti-Inflammatory and Antioxidative Effects of Sumatriptan Against Doxorubicin-Induced Cardiotoxicity in Rat

Abstract

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 the doxorubicin-induced cardiotoxicity. SumatriptanHT)1B/1D agonist that mainly used to relieve migraine pain, has suggested exerting protective effects in numerous pathological conditions through anti-inflammatory 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 anti-oxidative responses. Cardiotoxicity was induced by administration of doxorubicin 3 times a week (2.5 mg/kg i.p) for 2 consecutive weeks on male rats. The animals were divided in to the four group 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, inotropic 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 the 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 was increased in the doxorubicin-treated rats. This study illustrated protective effects of sumatriptan on decreasing doxorubicin-induced cardiac toxicity and mortality rate in part through inhibition of inflammatory and oxidative stress pathways.

Keywords

• Doxorubicin
• Sumatriptan
• Cardiotoxicity
• Oxidative stress
• Inflammation