Protective effects of magnesium sulfate against doxorubicin induced cardiotoxicity in rats

Clinical use of doxorubicin, an effective chemotherapeutic agent, has limited uses due to dose-dependent cardiac toxicity. It has been supposed that the production of free radicals and calcium ions overload can lead to cardiac toxicity. Magnesium is a cardioprotective drug which inhibits lipid peroxidation and reducing myocardial apoptosis. This study was aimed to explore the hypothesis that the cardiac toxicity induced by administration of doxorubicin is prevented or reduced by magnesium sulfate treatment and if so, whether this is associated with altered oxidative stress response in heart. Male Wistar rats were intraperitoneally injected with doxorubicin and magnesium sulfate and normal saline four times per week for 2 consecutive weeks. Then electrocardiographic, inotropic and biochemical tests were performed. Co-administration of magnesium sulfate with doxorubicin significantly reversed alterations in the stimulation threshold and contractile force induced by doxorubicin. In addition, magnesium sulfate improved body weight loss and alleviated the mortality rate of animals induced by doxorubicin. Moreover, it was observed that lesions induced by doxorubicin decreased in animals treated with magnesium sulfate. Magnesium sulfate significantly increased Glutathione (GSH) in doxorubicin treated animals. In conclusion, the results of the present study demonstrated that magnesium sulfate attenuate the cardio toxic effects of doxorubicin by increasing the activities of the antioxidants enzyme.