Doxorubicin-dependent lipid peroxidation at low partial pressures of O2.
Doxorubicin semiquinone, produced by reduction of doxorubicin with xanthine oxidase or ferredoxin reductase, reacted with H2O2 to cause deoxyribose oxidation that was catalysed by sub-micromolar concentrations of complexed iron. Both the mechanism of deoxyribose oxidation and the yield of oxidation products depended on the chelator. With EDTA or diethylenetriamine penta-acetic acid (DTPA), the reactive species behaved like free . OH. However, when ADP or no chelator was present, oxidation of deoxyribose was inhibited by mannitol but not benzoate or formate and was apparently not due to free . OH. Doxorubicin semiquinone and H2O2 caused peroxidation of phospholipid liposomes when ADP or no chelator was present, but not in the presence of EDTA or DTPA. Lipid peroxidation was iron dependent over a 0.1 to 1 microM range and was maximal with a pO2 of approximately 1.5 mm Hg, when the inhibitory effect of O2 on initiation is balanced by its stimulatory effects on propagation. The results imply that H2O2 and the doxorubicin semiquinone at low iron and O2 concentrations are very effective at initiating lipid peroxidation.
D000818:Animals; D002417:Cattle; D003855:Deoxyribose / Q000378:metabolism; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004492:Edetic Acid / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology*; D010313:Partial Pressure; D013482:Superoxide Dismutase / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000494:pharmacology
D008054:Lipid Peroxides; C024703:adriamycin semiquinone radicals; D003855:Deoxyribose; D004317:Doxorubicin; D004492:Edetic Acid; D006861:Hydrogen Peroxide; D007501:Iron; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D010100:Oxygen