Adriamycin and its iron(III) and copper(II) complexes. Glutathione-induced dissociation; cytochrome c oxidase inactivation and protection; binding to cardiolipin.
Some reactions of adriamycin (doxorubicin) and its Fe3+ and Cu2+ complexes were investigated with a view to understanding the mechanisms by which metal ion-adriamycin complexes damage cellular components. The ability of adriamycin in the presence of Cu2+ to inactivate the mitochondrial enzyme cytochrome c oxidase was effectively prevented by physiologic levels of glutathione. This result is explained by the observation that glutathione reacts with the Cu2+-adriamycin complex to produce free adriamycin. As sulfhydryl compounds are, in contrast, known to promote Fe3+-adriamycin-induced damage to cellular components, these results suggest that the response of a metal ion-adriamycin system to the presence of sulfhydryl compounds may be indicative of whether or not Cu2+-adriamycin is the damaging species. The partition of adriamycin into the octanol phase of an octanol-water two-phase system was greatly enhanced by the presence of cardiolipin. This result can be explained by the formation of a strong adriamycin-cardiolipin complex in the octanol phase which is one-half formed at an adriamycin concentration of 6 microM.
Hasinoff
B B
BB
Department of Chemistry, Memorial University of Newfoundland, St. John's, Canada.
Davey
J P
JP
D002308:Cardiolipins / Q000378:metabolism / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology*; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors*; D005290:Ferric Compounds / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology*; D012995:Solubility; D013482:Superoxide Dismutase / Q000494:pharmacology
D002308:Cardiolipins; D005290:Ferric Compounds; D009942:Organometallic Compounds; C053169:doxorubicin-copper(II) complex; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D003576:Electron Transport Complex IV; D005978:Glutathione