Mechanism of phospholipid peroxidation induced by ferric ion-ADP-adriamycin-co-ordination complex.
A system, which contains NADPH, purified cytochrome P-450 reductase and adriamycin, produces H2O2, O-2 and adriamycin semiquinone radical with O2 consumption and NADPH oxidation. This system, however, does not promote a peroxidation cleavage of unsaturated phospholipid. On the other hand, ferric ion-ADP-adriamycin-co-ordination complex, which may convert to a perferryl ion-co-ordination complex by an intramolecular electron transfer mechanism in air, acts as a powerful initiator for lipid peroxidation. A similar perferryl ion-co-ordination complex could also be produced from ferric ion-ADP-adriamycin-co-ordination complex after reducing it by NADPH-dependent cytochrome P-450 reductase in air.
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000818:Animals; D003574:Cytochrome c Group / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D005290:Ferric Compounds / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000494:pharmacology*; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D013053:Spectrophotometry
D003574:Cytochrome c Group; D005290:Ferric Compounds; D008054:Lipid Peroxides; D010743:Phospholipids; D000244:Adenosine Diphosphate; D004317:Doxorubicin; D007501:Iron; D009251:NADPH-Ferrihemoprotein Reductase