HEPATOTOXICITY OF MITOXANTRONE AND DOXORUBICIN
HEPATOTOXICITY OF MITOXANTRONE AND DOXORUBICIN
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DOI：
10.1016/0300-483x(90)90042-f
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发表时间：
1990-08-01
期刊：
影响因子：
4.5
通讯作者：
ARNAIZ, SL
中科院分区：
文献类型：
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作者：
LLESUY, SF;ARNAIZ, SL
阿霉素和米托蒽醌单次给药15 mg/kg体wt (i.p)，注射后第3、4、5天进行脂质过氧化测定。注射后第4天，米托蒽醌诱导肝脏自发化学发光增加155%，丙二醛水平和肝脏匀浆液过氧化氢引发化学发光增加73%和52%。注射后3天，阿霉素使肝脏自发化学发光和丙二醛形成分别增加51%和53%，但对肝脏匀浆中氢过氧化氢引发的化学发光没有影响。用阿霉素或米托蒽醌治疗小鼠，测定肝脏抗氧化酶水平。给予米托蒽醌可使铜锌超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活性分别降低50%、27%和42%。阿霉素也引起抗氧化酶水平的降低，但效果不太明显。我们的研究表明，米托蒽醌可能比阿霉素具有更大的肝毒性，其毒性机制可能涉及抗氧化防御的降低。
Doxorubicin and mitoxantrone were given to mice in a single dose of 15 mg/kg body wt (i.p.) and lipid peroxidation assays were carried out 3, 4 and 5 days after injection. Four days after injection, mitoxantrone induced an increase of 155% in liver spontaneous chemiluminescence and increases of 73% and 52% in malonaldehyde levels and hydroperoxide-initiated chemiluminescence of liver homogenates. Three days after injection, administration of doxorubicin produced increases of 51% and 53% in liver spontaneous chemiluminescence and malonaldehyde formation respetively, but no changes in hydroperoxide-initiated chemiluminescence of liver homogenates were observed. The hepatic levels of antioxidant enzymes were measured in mice treated with doxorubicin or mitoxantrone. Adminstration of mitoxantrone caused decreases of 50%, 27% and 42% in Cu-Zn superoxide dismutase, catalase and glutathione peroxidase activities, respectively. Doxorubicin also induced decreases in antioxidant enzyme levels but the effect was less marked. Our studies suggest that mitoxantrone might be more hepatotoxic than doxorubicin and that the mechanism of its toxicity would involve a reduction in antioxidant defenses.