Key Points
- To review the mechanisms by which adriamycin generates free radicals that cause cardiac toxicity.
- Reviewed biochemical literature evaluating the enzymatic activation of adriamycin (ADM) into reductive and oxidative semiquinone radical species.
- Analyzed the effects of reactive oxygen species, iron-chelating complexes, and membrane lipid peroxidation on cardiac mitochondrial function.
- Adriamycin is reduced by microsomal NADPH-P450 reductase and mitochondrial NADH dehydrogenase to a semiquinone radical, generating superoxide and hydroxyl radicals in the presence of oxygen.
- ADM extracts iron from ferritin to form an ADM-Fe3+ complex that induces lipid peroxidation, disrupting membrane integrity independently of superoxide dismutase or hydroxyl radical scavengers.
- Oxidative activation of ADM by peroxidases yields oxidative semiquinone radicals that inactivate critical mitochondrial enzymes, including succinate dehydrogenase and creatine kinase.
Structured PICO
IInterventionAdriamycin (doxorubicin)
OOutcomeMechanisms of cardiotoxicity
This review highlights the mechanistic role of free radicals, specifically reductive and oxidative semiquinone radicals, in mediating adriamycin-induced cardiotoxicity and mitochondrial dysfunction.