Julicher R H, Sterrenberg L, Bast A, Riksen R O, Koomen J M, Noordhoek J
J Pharm Pharmacol. 1986 Apr;38(4):277-82. doi: 10.1111/j.2042-7158.1986.tb04566.x.
Doxorubicin induces an acute cardiotoxicity that becomes manifest in isolated hearts as a deterioration in mechanical function. The oxidative component in this myocardial damage has been investigated. The effects of doxorubicin on the activity of superoxide dismutase and the capacity of the glutathione system, factors of the cellular protective mechanism against free radicals, were examined in rat isolated heart. Doxorubicin was found to reduce the capacity of the protective mechanisms. Whether oxidative membrane damage due to excessive free radical formation plays a role in the pathogenesis of the acute cardiotoxic action of doxorubicin was also examined. Its acute effect on myocardial contraction amplitude, frequency of beating, coronary flow and on the above mentioned biochemical parameters was compared in rat hearts sufficient or deficient in vitamin E. Peroxidation of lipids was measured as the formation of malondialdehyde, one of the final products of this process. Vitamin E deficiency neither aggravated the decrease in the capacity of the cellular protective factors nor worsened the reduction in myocardial function. Nor did induction of lipid peroxidation by doxorubicin occur in vitamin E-deficient hearts. It was concluded that lipid peroxidative damage most probably is not decisive in the development of the acute cardiomyopathy in rats.
阿霉素会引发急性心脏毒性，在离体心脏中表现为机械功能恶化。已对这种心肌损伤中的氧化成分进行了研究。在大鼠离体心脏中，检测了阿霉素对超氧化物歧化酶活性以及谷胱甘肽系统能力（细胞对抗自由基的保护机制因素）的影响。发现阿霉素会降低保护机制的能力。还研究了由于自由基过度形成导致的氧化膜损伤是否在阿霉素急性心脏毒性作用的发病机制中起作用。在维生素E充足或缺乏的大鼠心脏中，比较了阿霉素对心肌收缩幅度、心跳频率、冠状动脉血流量以及上述生化参数的急性影响。脂质过氧化以丙二醛的形成来衡量，丙二醛是该过程的最终产物之一。维生素E缺乏既没有加重细胞保护因子能力的下降，也没有使心肌功能的降低恶化。在维生素E缺乏的心脏中，阿霉素也没有诱导脂质过氧化。得出的结论是，脂质过氧化损伤很可能在大鼠急性心肌病的发展中不起决定性作用。
