Lores Arnaiz S, Llesuy S
Institute of Biochemistry and Biophysics, School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
Toxicology. 1993 Jan 29;77(1-2):31-8. doi: 10.1016/0300-483x(93)90135-f.
Doxorubicin and mitoxantrone were given to mice in a single dose of 15 mg/kg body wt (i.p.). 'In situ' heart spontaneous chemiluminescence, hydroperoxide-initiated chemiluminescence and TBARS were measured in heart homogenates of treated and control animals at 2-5 days after injection. Heart spontaneous emission (control value: 45 +/- 5 cps/cm2) was increased by 10-fold in doxorubicin-treated mice 4 days after administration, whereas mitoxantrone did not produce any significant change. Administration of doxorubicin produced increases of 50% in hydroperoxide-initiated chemiluminescence and of 80% in TBARS levels 4 days after injection. Mitoxantrone did not induce significant changes in these parameters as compared with the controls. Cardiac reduced glutathione levels were not affected by mitoxantrone but were decreased (about 30%) by doxorubicin (control value: 0.98 +/- 0.08 mumol/g organ). Our data indicate that mitoxantrone does not induce an increase in the endogenous lipoperoxidation rate in heart tissue as doxorubicin does; this could contribute to the lower cardiotoxicity of mitoxantrone as compared with doxorubicin.
将阿霉素和米托蒽醌以15毫克/千克体重的单次剂量腹腔注射给小鼠。在注射后2至5天，测量处理组和对照组动物心脏匀浆中的“原位”心脏自发化学发光、氢过氧化物引发的化学发光以及硫代巴比妥酸反应产物（TBARS）。给药4天后，阿霉素处理的小鼠心脏自发发射（对照值：45±5 cps/cm²）增加了10倍，而米托蒽醌未产生任何显著变化。注射阿霉素4天后，氢过氧化物引发的化学发光增加了50%，TBARS水平增加了80%。与对照组相比，米托蒽醌未诱导这些参数的显著变化。心脏中还原型谷胱甘肽水平不受米托蒽醌影响，但阿霉素使其降低（约30%）（对照值：0.98±0.08微摩尔/克器官）。我们的数据表明，米托蒽醌不像阿霉素那样诱导心脏组织内源性脂质过氧化率增加；这可能是米托蒽醌与阿霉素相比心脏毒性较低的原因。
