Sarvazyan N A, Askari A, Huang W H
Dept. of Physiology, Texas Tech University Health Science Center, Lubbock 79430, USA.
Life Sci. 1995;57(10):1003-10. doi: 10.1016/0024-3205(95)02036-i.
Our previous studies have shown that isolated adult rat cardiomyocytes with normal and reduced Cu/Zn SOD activities are equally susceptible to extracellularly generated oxidants (hydrogen peroxide, glucose oxidase/glucose and xanthine oxidase/xanthine systems). In the present study we exposed myocytes with reduced SOD activity to doxorubicin (adriamycin). Cardiotoxicity of doxorubicin has been attributed to the production of superoxide anion inside the cell. Cardiomyocytes with reduced SOD activity, but normal ATP content and viability, were obtained by the treatment of isolated cells with diethyldithiocarbamate (DDC). DDC-treated myocytes were significantly less resistant to doxorubicin than controls. Doxorubicin-stimulated superoxide anion formation, measured by the rate of SOD-inhibitable acetylated cytochrome C reduction, was significantly higher in the cytosolic fraction of DDC-treated cells compared to controls. These results indicate that for isolated cardiac myocytes an essential part of cytotoxicity of doxorubicin can be explained by the formation of superoxide anion and that the level of intracellular SOD activity should be considered as a significant factor for cell protection.
我们之前的研究表明，铜锌超氧化物歧化酶（Cu/Zn SOD）活性正常和降低的成年大鼠离体心肌细胞，对细胞外产生的氧化剂（过氧化氢、葡萄糖氧化酶/葡萄糖和黄嘌呤氧化酶/黄嘌呤系统）的敏感性相同。在本研究中，我们将SOD活性降低的心肌细胞暴露于阿霉素（ Adriamycin）。阿霉素的心脏毒性归因于细胞内超氧阴离子的产生。通过用二乙基二硫代氨基甲酸盐（DDC）处理分离的细胞，获得了SOD活性降低但ATP含量和活力正常的心肌细胞。与对照组相比，DDC处理的心肌细胞对阿霉素的抵抗力明显更低。通过SOD可抑制的乙酰化细胞色素C还原速率测量，DDC处理的细胞胞质部分中阿霉素刺激的超氧阴离子形成明显高于对照组。这些结果表明，对于离体心肌细胞，阿霉素细胞毒性的一个重要部分可以通过超氧阴离子的形成来解释，并且细胞内SOD活性水平应被视为细胞保护的一个重要因素。
