Generation of free radical by interaction of iron with thiols in human plasma and its possible significance

It has been reported that iron can generate reactive oxygen species (ROS) with thiols. In this study, we examined the interaction of iron with thiols in plasma and the generation of ROS. In human plasma, unlike with Fe3+, treatment with Fe2+ increased lucigenin-enhanced chemiluminescence in a concentration-dependent manner, and this was inhibited by superoxide dismutase. Boiling of plasma did not affect chemiluminescence generation induced by Fe2+. Thiol depletion in plasma by pretreatment with N-ethylmaleimide (NEM) decreased chemiluminescence significantly. Consistent with these findings, albumin, the major thiol contributor in plasma, also generated ROS with Fe2+. Treatment with Fe2+ resulted in significant reduction of oxygen radical absorbance capacity (ORAC value) in plasma followed by an increase in low-density lipoprotein (LDL) oxidation. These results suggest that generation of ROS by nonenzymatic reaction of Fe2+ with plasma thiols could lead to reduction of total antioxidant capacity in plasma, thereby enhancing susceptibility of plasma LDL to oxidation under iron overload conditions.