Attenuation of cardiotoxicity of daunomycin using a complex with heparin.
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.
Mizuno
Y
Y
Department of Pediatrics, Kyushu University, Fukuoka, Japan.
Hara
T
T
Kawaoto
H
H
Ueda
K
K
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000633:toxicity*; D006224:Cricetinae; D003630:Daunorubicin / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000633:toxicity*; D006331:Heart Diseases / Q000139:chemically induced*; D006493:Heparin / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D008647:Mesocricetus; D051379:Mice; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D006493:Heparin; D003630:Daunorubicin