Paraquat and iron-dependent lipid peroxidation. NADPH versus NADPH-generating systems

The aim of this work was to study the effect of paraquat (P2+) on NADPH iron-dependent lipid peroxidation (basal peroxidation) either in the presence of NADPH or in the presence of NADPH-generating systems. When NADPH is present, P2+ potentiates NADPH iron-dependent lipid peroxidation, but use of NADPH-generating systems cancels this effect. This may be attributed to certain components in NADPH-generating systems such as glucose-6-phosphate and sodium isocitrate, which act as iron chelators. The binding of iron by these molecules facilitates its reduction and enhances its reactivity toward dioxygen molecules, leading to the formation of reactive species capable of initiating lipid peroxidation, such as Fe3+-O2-*. Under these conditions of rapid basal peroxidation, any additional reduction of iron(III) by a reduced form of P2+ (P+*) has no apparent effect on the peroxidation itself, probably because the initial reaction between iron(II) and O2 followed by initiation of the peroxidation are both rate-limiting steps in the process. Consequently, any alteration of the composition of the reacting mixture (e.g., buffers or the generating system) must be taken into consideration because the formation of new iron chelates can change the rate of basal peroxidation and will modify the effect of redoxcycling molecules.