DOXORUBICIN-HEPARIN COMPLEX - REDUCTION OF CARDIOTOXICITY OF DOXORUBICIN

We have compared the antitumor activity and cardiotoxicity of free dox orubicin (Dox) and doxorubicin-heparin complex in vivo and in vitro. D ox and Dox-heparin complex equally inhibited the DNA synthesis of leuk emic cells and showed a similar anticancer activity against tumor-bear ing mice. Acute toxicity of Dox at the dose of 20 mg/kg or 30 mg/kg wa s significantly more profound than that of the Dox-heparin complex, wh ich was demonstrated by survival rate (P <0.01). Chronic toxicities of Dox and the Dox-heparin complex were compared by giving the respectiv e 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 Do x alone (P <0.01). The pathological damage to the cardiac tissue in mi ce heated 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 D ox without reducing its antitumor activity in mice, and suggests a pos sible clinical application of Dox-heparin complex in humans.