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.
Flandina
C
C
Istituto di Farmacologia, Policlinico P. Giaccone, Palermo, Italy.
Sanguedolce
R
R
Rausa
L
L
D'Alessandro
N
N
D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D007275:Injections, Intravenous; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051379:Mice; D011292:Premedication; D011785:Quality Assurance, Health Care; D011929:Razoxane / Q000494:pharmacology*
D011929:Razoxane; D004317:Doxorubicin; D007545:Isoproterenol