Is Superoxide an Initiator of Microsomal Lipid Peroxidation?

The effects of "pro-oxidant" quinones, doxorubicin, Fe3+-ADP-doxorubicin complex, and menadione, as well as of free radical scavengers possessing superoxide-dismuting activities, Fe3+-rutin and Cu2+-rutin, on super-oxide production and lipid peroxidation in rat liver microsomes have been studied. All quinone compounds efficiently suppressed lucigenin-dependent chemiluminesceace produced in NADPH-dependent microsomal lipid peroxidation, but exhibited different effects on cytochrome c reduction: doxorubicin and Fe3+-ADP- doxorubicin weakly inhibited and menadione enhanced it. In accord with previous findings, menadione inhibited malondialdehyde (MDA) formation in microsomes, while Fe3+-ADP-doxorubicin enhanced it. Efficiency of inhibition of MDA formation by the Fe3+-rutin and Cu2+- rutia complexes correlated well with their superoxidedismuting activities in contrast to the findings obtained in nonenzymatic liposomal peroxidation, where the formation of superoxide ion is not expected. On these grounds, we propose that superoxide ion is an obligatory initiation species in microsomal lipid peroxidation; the effects of pro-oxidant quinones on lipid peroxidation depends on their ability to chelate iron ions and not on their redox-cycling activities.