Schinetti M L, Rossini D, Bertelli A
J Cancer Res Clin Oncol. 1987;113(1):15-9. doi: 10.1007/BF00389961.
Human neutrophils exposed to 10(-4) M doxorubicin and the derivatives epirubicin and thepirubicin revealed a different intracellular penetration and distribution pattern as demonstrated by fluorescence microscopy and fluorimetric determination of drug intracellular concentration. While doxorubicin was found to be a potent inducer of superoxide generation from resting cells, epirubicin exhibited less superoxide-inducing power. Thepirubicin on the contrary did not show any superoxide-inducing effect. Moreover the anthracyclines tested all inhibited the phorbol ester-stimulated chemiluminescent response to the same extent, which suggested a common target for the drug action. Anthracycline-stimulated superoxide production seems to correlate with the cardiotoxic effects. The most cardiotoxic drug, doxorubicin, is the most potent inducer of superoxide generation, while epirubicin, which is less cardiotoxic, has a relatively limited effect on superoxide production. Thepirubicin which has been shown not to induce delayed cardiomyopathy has no effect on superoxide release from the cells.
通过荧光显微镜和药物细胞内浓度的荧光测定法表明，暴露于10(-4)M阿霉素及其衍生物表柔比星和吡柔比星的人中性粒细胞呈现出不同的细胞内渗透和分布模式。虽然发现阿霉素是静息细胞中超氧化物生成的有效诱导剂，但表柔比星的超氧化物诱导能力较弱。相反，吡柔比星未显示出任何超氧化物诱导作用。此外，所测试的蒽环类药物均在相同程度上抑制佛波酯刺激的化学发光反应，这表明药物作用存在共同靶点。蒽环类药物刺激的超氧化物产生似乎与心脏毒性作用相关。心脏毒性最强的药物阿霉素是超氧化物生成的最有效诱导剂，而心脏毒性较小的表柔比星对超氧化物产生的影响相对有限。已证明不会诱发迟发性心肌病的吡柔比星对细胞中超氧化物释放没有影响。
