Brain and Spinal Cord Injury Research Center, Neuroscience Institute Tehran University of Medical Sciences, Tehran, Iran.
Department of Pathology, Imam Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Life Sci. 2018 Aug 15;207:436-441. doi: 10.1016/j.lfs.2018.06.022. Epub 2018 Jun 22.
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.
多柔比星是一种有效的化疗药物,但由于剂量依赖性心脏毒性,其临床应用受到限制。据推测,自由基的产生和钙离子超载可导致心脏毒性。镁是一种具有心脏保护作用的药物,可抑制脂质过氧化和减少心肌细胞凋亡。本研究旨在探讨以下假设,即通过硫酸镁治疗可预防或减轻多柔比星引起的心脏毒性,以及如果是这样,这种作用是否与心脏氧化应激反应的改变有关。
雄性 Wistar 大鼠每周腹腔内注射多柔比星和硫酸镁 4 次,连续 2 周,然后进行心电图、变力和生化测试。
硫酸镁与多柔比星联合使用可显著逆转多柔比星引起的刺激阈值和收缩力的改变。此外,硫酸镁改善了多柔比星引起的体重减轻和动物死亡率。此外,还观察到硫酸镁处理的动物的损伤减少。硫酸镁显著增加了多柔比星处理动物的谷胱甘肽(GSH)。
总之,本研究结果表明,硫酸镁通过增加抗氧化酶的活性来减轻多柔比星的心脏毒性作用。