Mechanisms of anthracycline - induced cardiac toxicity: The role of iron binding

Abstract

Adriamycin and related anthracyclines are powerful antineoplastic agents, whose use is time limited by dose dependent cardiac toxicity. Adriamycin targets three components of cardiac muscle cells; the nucleus, the mitochondria and the sarcoplasmic membrane/tubular systems. The anti-tumour effect and cardiac toxicity of adriamycin involve different pathways. A biochemical and electron microscopic study of the cardiac toxicity of adriamycin in a mouse model indicate that binding of iron by adriamycin causes alterations in several enzyme pathways and increases free radical generation, all of which depend on the bioavailability of iron. ICRF-187 (ADR-529) removes iron from the adriamycin-iron complex, resulting in a cardioprotective effect.