Villani F, Galimberti M, Poggi P, Rozza A, Lanza E, Favalli L, Scavini C
Divisione di Fisiopatologia Cardiorespiratoria, Istituto Nazionale Tumori, Milano.
Cardiologia. 1992 Oct;37(10):709-11.
The production of oxygen-free radicals has been proposed as a determinant of the delayed toxicity of doxorubicin. The aim of the present investigation was to evaluate the potential cardioprotective effect of superoxide dismutase (SOD) and catalase (CAT) 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 or CAT were administered intravenously at the dose of 10000 U/kg 2 min before and 30 min after each DXR administration. Cardiac toxicity was monitored by means of electrocardiography (QaT interval) and by light and electron microscopy evaluation of left ventricle fragments. DXR treated rats showed, in comparison with control animals, a decrease of body weight gain, a progressive and irreversible prolongation of QaT and significant morphologic lesions consisting in myocyte vacuolization and myofibrillar loss. SOD significantly prevented the impairment of body weight gain and QaT prolongation. Moreover, morphologic lesions were significantly reduced in rats receiving DXR + SOD. On the contrary, CAT seems to be completely devoid of protective effect.
已有研究提出，氧自由基的产生是阿霉素延迟毒性的一个决定因素。本研究的目的是评估超氧化物歧化酶（SOD）和过氧化氢酶（CAT）对阿霉素（DXR）诱导的大鼠模型延迟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的DXR，共4周。在每次DXR给药前2分钟和给药后30分钟，以10000 U/kg的剂量静脉注射SOD或CAT。通过心电图（QaT间期）以及左心室切片的光学和电子显微镜评估来监测心脏毒性。与对照动物相比，接受DXR治疗的大鼠体重增加减少，QaT逐渐且不可逆地延长，并且存在明显的形态学病变，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和QaT延长。此外，接受DXR + SOD的大鼠形态学病变明显减少。相反，CAT似乎完全没有保护作用。
