OXIDATIVE STRESS IN MOUSE HEART BY ANTITUMORAL DRUGS - A COMPARATIVE-STUDY OF DOXORUBICIN AND MITOXANTRONE
OXIDATIVE STRESS IN MOUSE HEART BY ANTITUMORAL DRUGS - A COMPARATIVE-STUDY OF DOXORUBICIN AND MITOXANTRONE
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DOI：
10.1016/0300-483x(93)90135-f
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发表时间：
1993-01-29
期刊：
影响因子：
4.5
通讯作者：
LLESUY, S
中科院分区：
文献类型：
--
作者：
ARNAIZ, SL;LLESUY, S
多柔比星和米托蒽醌以15 mg/kg体重的单剂量（i. p.）给予nice。在注射后2-5天，在治疗和对照动物的心脏匀浆中测量“原位”心脏自发化学发光、过氧化氢引发的化学发光和TBARS。 心脏自发辐射（对照值：45 +/- 5 cps/cm 2）增加了10倍多柔比星治疗的小鼠给药后4天，而米托蒽醌没有产生任何显着的变化。注射阿霉素4天后，过氧化氢引发的化学发光增加50%，TBARS水平增加80%。与对照组相比，米托蒽醌未引起这些参数的显著变化。心脏还原型谷胱甘肽水平不受米托蒽醌的影响，但多柔比星（对照值：0.98 +/- 0.08 mumol/g器官）降低（约30%）。我们的数据表明，米托蒽醌不诱导心脏组织中的内源性脂质过氧化率增加阿霉素，这可能有助于降低心脏毒性的米托蒽醌相比，阿霉素。
Doxorubicin and mitoxantrone were given to nice 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.