Ameliorative effects of ICRF-187 [(+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane] on the cardiotoxicity induced by doxorubicin or by isoproterenol in the mouse.

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.