Mizuno Y, Hara T, Kawaoto H, Ueda K
Department of Pediatrics, Kyushu University, Fukuoka, Japan.
Int J Hematol. 1996 Jan;63(1):25-31. doi: 10.1016/0925-5710(95)00417-3.
Daunomycin (DM) is one of the most important antitumor agents. However, the cardiotoxicity of DM limits it's clinical use. We have made an ionic complex with heparin to decrease the cardiotoxicity. Cardiotoxicities of DM and DM-heparin complex were compared in hamsters. On the electrocardiogram (ECG), two of the four hamsters given DM showed the serious abnormality, bidirectional ventricular premature contraction, while the hamsters given DM-heparin or saline had no abnormalities. On pathological examination, cardiac tissue in hamsters given DM showed deposition of basophilic materials, mild eosinophilic change of myofibrils and microvascuolization, whereas no change was observed in hamsters given DM-heparin complex or saline. Acute toxic effects on survival rates and body weights were more profound in DM-infused mice than in DM-heparin-infused mice. DM and DM-heparin complex showed similar anticancer activity both in vivo and in vitro. Thus, the present study suggests that the DM-heparin complex may attenuate the cardiotoxicity of DM without affecting it's antitumor effect in humans.
柔红霉素（DM）是最重要的抗肿瘤药物之一。然而，DM的心脏毒性限制了其临床应用。我们制备了一种与肝素的离子复合物以降低心脏毒性。在仓鼠中比较了DM和DM-肝素复合物的心脏毒性。在心电图（ECG）上，给予DM的四只仓鼠中有两只出现严重异常，双向室性早搏，而给予DM-肝素或生理盐水的仓鼠没有异常。病理检查显示，给予DM的仓鼠心脏组织出现嗜碱性物质沉积、肌原纤维轻度嗜酸性改变和微血管化，而给予DM-肝素复合物或生理盐水的仓鼠未观察到变化。DM注射小鼠对存活率和体重的急性毒性作用比DM-肝素注射小鼠更明显。DM和DM-肝素复合物在体内和体外均表现出相似的抗癌活性。因此，本研究表明，DM-肝素复合物可能在不影响其对人类抗肿瘤作用的情况下减轻DM的心脏毒性。
