Flandina C, Sanguedolce R, Rausa L, D'Alessandro N
Istituto di Farmacologia, Policlinico P. Giaccone, Palermo, Italy.
Res Commun Chem Pathol Pharmacol. 1990 Dec;70(3):259-72.
CD 1 female mice were treated with Doxorubicin (5 mg/Kg i.v.) once a week for 8 weeks or with Isoproterenol (20 mg/Kg s.c.) once a week for 5 weeks. Other mice were treated with the chelating agent ICRF-187 (100 mg/Kg i.p.) 30 min. before Doxorubicin or Isoproterenol administration. The animals were sacrificed 4 weeks after the last administration and their cardiac morphology was evaluated by means of light microscopy. ICRF-187 significantly lessened the extent and the severity of the cardiac lesions by Doxorubicin (-68%, P less than 0.01 in left atrium; -69%, P less than 0.01 in ventricles) and the extent of those induced by Isoproterenol (-56%, P less than 0.05). These data confirm that ICRF-187 has good activity on Doxorubicin-induced myocardiopathy and provide new information about the "in vivo" effects of the compound on the cardiotoxicity caused by Isoproterenol. Moreover, they seem to confirm that a common event, probably the involvement of metal ions, plays a role in the morphologically different myocardiopathies induced by Doxorubicin or Isoproterenol.
给雌性CD1小鼠静脉注射阿霉素（5毫克/千克），每周一次，共8周；或皮下注射异丙肾上腺素（20毫克/千克），每周一次，共5周。其他小鼠在给予阿霉素或异丙肾上腺素前30分钟腹腔注射螯合剂ICRF - 187（100毫克/千克）。在最后一次给药4周后处死动物，通过光学显微镜评估其心脏形态。ICRF - 187显著减轻了阿霉素所致心脏病变的程度和严重性（左心房减轻68%，P<0.01；心室减轻69%，P<0.01）以及异丙肾上腺素所致病变的程度（减轻56%，P<0.05）。这些数据证实ICRF - 187对阿霉素诱导的心肌病具有良好活性，并提供了该化合物对异丙肾上腺素所致心脏毒性“体内”作用的新信息。此外，这些数据似乎证实了一个共同事件，可能是金属离子的参与，在阿霉素或异丙肾上腺素诱导的形态不同的心肌病中起作用。
