Pierściński G, Drzewoski J, Nowak D
Department of Clinical Pharmacology, Medical Academy, Lódź, Poland.
Pol J Pharmacol. 1994 Jan-Apr;46(1-2):55-9.
Influence of doxorubicin (DOX) and its less cardiotoxic analog 4'-epi-doxorubicin (EPI) on the peroxidation of cellular components was evaluated in vivo. Previous experimental work performed at our laboratory indicates that DOX, but not EPI, induces a marked increase in conjugated dienes formation (CD) in mice hearts exposed to a single intravenous dose (30 mg/kg) of that drug. Therefore, in the present study lipid peroxidation after treatment with these anthracyclines, was evaluated and compared in vivo by measuring the content of malondialdehyde (MDA) in heart, liver and lungs of Balb/c mice over 48-h period at various time-points: 5, 24 and 48 h after a single intravenous injection of either DOX or EPI. A statistically significant increased formation of MDA was found after both DOX and EPI in mice heart, lung and liver homogenates. DOX caused a relatively higher increase in MDA formation than did EPI. The results obtained in this study indicate that both DOX and EPI induce peroxidation of tissue components in vivo as shown by the increase in the formation of MDA. However, only DOX induces significant increase in lipid peroxidation in cardiac muscle, as assessed by the formation of CD. The results also suggest that peroxidation of other tissue components may be responsible for anthracycline-induced cardiotoxicity.
在体内评估了阿霉素（DOX）及其心脏毒性较小的类似物4'-表阿霉素（EPI）对细胞成分过氧化的影响。我们实验室之前进行的实验工作表明，DOX而非EPI会使单次静脉注射（30 mg/kg）该药物的小鼠心脏中共轭二烯形成（CD）显著增加。因此，在本研究中，通过在不同时间点（单次静脉注射DOX或EPI后的5、24和48小时）测量Balb/c小鼠心脏、肝脏和肺中丙二醛（MDA）的含量，对这些蒽环类药物治疗后的体内脂质过氧化进行了评估和比较。在小鼠心脏、肺和肝脏匀浆中，DOX和EPI处理后均发现MDA形成有统计学意义的增加。DOX导致的MDA形成增加相对高于EPI。本研究获得的结果表明，如MDA形成增加所示，DOX和EPI在体内均诱导组织成分的过氧化。然而，通过CD形成评估，只有DOX会导致心肌脂质过氧化显著增加。结果还表明，其他组织成分的过氧化可能是蒽环类药物诱导心脏毒性的原因。
