Doxorubicin-heparin complex: reduction of cardiotoxicity of doxorubicin.
We have compared the antitumor activity and cardiotoxicity of free doxorubicin (Dox) and doxorubicin-heparin complex in vivo and in vitro. Dox and Dox-heparin complex equally inhibited the DNA synthesis of leukemic cells and showed a similar anticancer activity against tumor-bearing mice. Acute toxicity of Dox at the dose of 20 mg/kg or 30 mg/kg was significantly more profound than that of the Dox-heparin complex, which was demonstrated by survival rate (P < 0.01). Chronic toxicities of Dox and the Dox-heparin complex were compared by giving the respective reagent (2 mg/kg) weekly for 20 weeks. The weight gains of the mice given Dox-heparin complex were greater than those of the mice given Dox alone (P < 0.01). The pathological damage to the cardiac tissue in mice treated with Dox-heparin complex was significantly less severe than that of mice treated with Dox. Thus, the present study indicates that complexing with heparin diminished the acute and chronic toxicity of Dox without reducing its antitumor activity in mice, and suggests a possible clinical application of Dox-heparin complex in humans.
Mizuno
Y
Y
Department of Pediatrics, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Hara
T
T
Tachibana
S
S
Uragoh
K
K
Akazawa
K
K
Ueda
K
K
D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004338:Drug Combinations; D004354:Drug Screening Assays, Antitumor; D006321:Heart / Q000187:drug effects*; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000473:pathology; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004338:Drug Combinations; D004317:Doxorubicin; D006493:Heparin