D'Alessandro N, Nicotra C, Crescimanno M, Rausa L
Institute of Pharmacology, P. Giaccone Polyclinic, Palermo, Sicily.
Drugs Exp Clin Res. 1987;13(10):601-6.
The behaviour of heart and liver catalase was studied 4 days after the administration of different doxorubicin doses to CD 1 mice. The antiblastic increased the specific activity of the heart enzyme with a clear dose-response relationship (+27% after 5 mg/kg i.p.; +61% after 7 mg/kg; + 108% after 10 mg/kg; + 147% after 15 mg/kg). This did not occur in the liver where, on the contrary, a significant reduction of catalase (-31%) was noticed after the highest dose. Analyses by gel filtration excluded the possibility that doxorubicin induces major changes in the molecular properties of heart catalase. In vivo experiments with aminotriazole, which blocks catalase irreversibly, indicated that doxorubicin stimulates the synthesis of cardiac catalase. These findings are discussed with reference to the possible mechanisms of anthracycline cardiotoxicity. The catalase elevation could represent a reaction by the heart to free radicals generated by doxorubicin.
在给CD 1小鼠注射不同剂量阿霉素4天后，对心脏和肝脏过氧化氢酶的行为进行了研究。抗增殖作用使心脏酶的比活性增加，呈现明显的剂量反应关系（腹腔注射5 mg/kg后增加27%；7 mg/kg后增加61%；10 mg/kg后增加108%；15 mg/kg后增加147%）。肝脏中未出现这种情况，相反，在最高剂量后，过氧化氢酶显著降低（-31%）。凝胶过滤分析排除了阿霉素诱导心脏过氧化氢酶分子特性发生重大变化的可能性。用氨基三唑进行的体内实验表明，氨基三唑可不可逆地阻断过氧化氢酶，该实验表明阿霉素刺激心脏过氧化氢酶的合成。结合蒽环类药物心脏毒性的可能机制对这些发现进行了讨论。过氧化氢酶升高可能代表心脏对阿霉素产生的自由基的一种反应。
