Villani F, Galimberti M, Favalli L, Rozza A, Lanza E, Poggi P
Divisione di Fisopatologia Cardiorespiratoria, Istituto Nazionale per lo Studio e la Cura dei Tumori di Milano.
G Ital Cardiol. 1991 Jun;21(6):633-41.
The production of oxygen free radicals during anthracycline therapy has been proposed as a determinant of the toxicity of anthracyclines. Oxygen radical generation might specifically affect the myocardium because of the low antioxidant defense systems in cardiac tissue. The aim of the present investigations was to evaluate the potential cardioprotective effect of superoxide dismutase (SOD) against the delayed cardiomyopathy induced by doxorubicin (DXR) in a rat model. Female Sprague Dawley rats received 3 mg/kg of DXR intravenously weekly for 4 weeks. SOD was administered intravenously at the dose of 10,000 U/Kg one minute before and 30 minutes after each DXR administration. Cardiac toxicity was monitored in vivo by means of electrocardiography (QaT interval), by determining the contractile properties of isolated atria, and by light and electron microscopy evaluation of left ventricle fragments excised 5 weeks after the last DXR administration. The degree of morphologic lesions was quantitated according to the score system proposed by E. Billingham. DXR treated rats showed, in comparison with control animals treated with saline a decrease of body weight gain, a progressive and irreversible prolongation of QaT, decrease of contractility of isolated atria, and significant morphologic lesions consisting in myocyte vacuolization and myofibrillar loss. SOD significantly prevented the impairment of body weight gain, QaT prolongation and the impairment of myocardial contractility. Moreover morphologic lesions were significantly reduced in rats receiving DXR + SOD. The present data indicate that SOD could represent an important issue in myocardial protection against DXR cardiotoxicity.
蒽环类药物治疗期间氧自由基的产生被认为是蒽环类药物毒性的一个决定因素。由于心脏组织中抗氧化防御系统较低，氧自由基的产生可能会特异性地影响心肌。本研究的目的是评估超氧化物歧化酶（SOD）对阿霉素（DXR）诱导的大鼠模型迟发性心肌病的潜在心脏保护作用。雌性Sprague Dawley大鼠每周静脉注射3 mg/kg DXR，共4周。在每次DXR给药前1分钟和给药后30分钟静脉注射剂量为10,000 U/Kg的SOD。通过心电图（QaT间期）、测定离体心房的收缩特性以及在最后一次DXR给药5周后对切除的左心室片段进行光镜和电镜评估，在体内监测心脏毒性。根据E. Billingham提出的评分系统对形态学损伤程度进行定量。与用生理盐水处理的对照动物相比，DXR处理的大鼠体重增加减少、QaT进行性不可逆延长、离体心房收缩力降低，并且存在明显的形态学损伤，包括心肌细胞空泡化和肌原纤维丧失。SOD显著预防了体重增加受损、QaT延长和心肌收缩力受损。此外，接受DXR + SOD的大鼠形态学损伤明显减轻。目前的数据表明，SOD可能是心肌保护免受DXR心脏毒性的一个重要因素。
