Self-reduction of the iron(III)-doxorubicin complex.
The Fe3(+)-doxorubicin complex undergoes reactions that suggest that the complex self-reduces to a ferrous oxidized-doxorubicin free radical species. The Fe3(+)-doxorubicin system is observed to reduce ferricytochrome c, consume O2 and react with 2,2'-bipyridine. Bipyridine acts as a "ferrous ion scavenger" as it reacts with the ferrous ion produced by Fe3(+)-doxorubicin self-reduction. In the absence of O2, a ferrous doxorubicin complex accumulates. In the presence of oxygen, Fe2+ recycles back to Fe3+. The rates of these reactions were measured and the Fe3(+)-doxorubicin self-reduction was determined to be the rate-determining step. The Fe3(+)-doxorubicin induced inactivation of cytochrome c oxidase and NADH cytochrome c reductase on beef heart submitochondrial particles occurs at a rate similar to Fe3(+)-doxorubicin self-reduction. Thus the rate at which damage to these mitochondrial enzymes occurs may be controlled by a nonenzymatic Fe3(+)-doxorubicin self-reduction.
Hasinoff
B B
BB
Department of Chemistry and Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
D000332:Aerobiosis; D000818:Animals; D002374:Catalase / Q000494:pharmacology; D002417:Cattle; D003574:Cytochrome c Group / Q000378:metabolism; D004317:Doxorubicin / Q000378:metabolism*; D005296:Ferrous Compounds / Q000378:metabolism*; D005609:Free Radicals; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D010100:Oxygen / Q000493:pharmacokinetics; D013482:Superoxide Dismutase / Q000494:pharmacology
D003574:Cytochrome c Group; D005296:Ferrous Compounds; D005609:Free Radicals; D004317:Doxorubicin; D010088:Oxidoreductases; D002374:Catalase; D013482:Superoxide Dismutase; D010100:Oxygen