Sugiyama S, Yamada K, Hayakawa M, Ozawa T
Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya, Japan.
Biochem Mol Biol Int. 1995 Aug;36(5):1001-7.
This experiment was designed to evaluate whether or not liposomal encapsulated-doxorubicin and combination therapy of free doxorubicin with coenzyme Q10, an antioxidant, mitigate the delayed adverse effects on cardiac muscle mitochondria. Rats aged 7 weeks were divided into the following four groups; rats were injected with doxorubicin or liposomal encapsulated-doxorubicin, total dose 15 mg/kg. The doxorubicin group consisted of two subgroups depending on diet, i.e., standard diet or 0.2% coenzyme Q10 diet. Mitochondria from cardiac muscles were prepared from rats aged 13 and 35 weeks. No significant decrease in the activity of complex I of the mitochondrial electron transport chain was observed in rats aged 13 weeks among the groups, however, significant decreases in the activity in rats aged 35 weeks were observed in the doxorubicin and liposomal doxorubicin groups compared with the corresponding control rats. In contrast, no significant change in complex I activity was observed in rats fed with coenzyme Q10 diet irrespective of doxorubicin treatment. From these results, not liposomal encapsulation of doxorubicin but combination therapy with antioxidant might be expected to reduce the delayed adverse effects of doxorubicin on heart mitochondria.
本实验旨在评估脂质体包裹的阿霉素以及游离阿霉素与抗氧化剂辅酶Q10的联合治疗是否能减轻对心肌线粒体的延迟性不良反应。将7周龄的大鼠分为以下四组；给大鼠注射阿霉素或脂质体包裹的阿霉素，总剂量为15mg/kg。根据饮食，阿霉素组分为两个亚组，即标准饮食组或0.2%辅酶Q10饮食组。从13周龄和35周龄的大鼠中制备心肌线粒体。在13周龄的大鼠中，各组线粒体电子传递链复合体I的活性均未观察到显著下降，然而，与相应的对照大鼠相比，在35周龄的大鼠中，阿霉素组和脂质体阿霉素组的活性显著下降。相比之下，无论阿霉素治疗如何，喂食辅酶Q10饮食的大鼠复合体I活性均未观察到显著变化。从这些结果来看，可能预期不是阿霉素的脂质体包裹，而是与抗氧化剂的联合治疗可减少阿霉素对心脏线粒体的延迟性不良反应。
