Ascorbyl free radical reflects catalytically active iron after intravenous iron saccharate injection

Iron release from intravenous iron formulations can increase both non-transferrin-bound iron (NTBI) and oxidative stress. However, data showing a direct association between these parameters are sparse. The aim of this study was to adapt a recently published electron spin resonance (ESR) method to measure NTBI after iron injection and further to investigate its correlation to levels of oxidative stress markers. Twenty chronic hemodialysis patients were enrolled. NTBI and markers of oxidative stress, ascorbyl free radical (AFR), oxidized LDL, protein carbonyl, total antioxidant capacity, and myeloperoxidase, were measured in blood samples collected before and after intravenous injection of 100 mg iron saccharate. NTBI and all analyzed oxidative stress markers were increased 10 min after iron injection. Specifically, NTBI rose by 375% and AFR by 40%. Significant increases in these parameters were still seen 60 min after the injection. The changes in NTBI and AFR were closely correlated. The close correlation between intravascular release of NTBI and increase in plasma AFR after iv iron injection, as well as the increase in all measured oxidative stress markers, suggests that the iron measured was catalytically active. The ESR method was sufficiently sensitive and robust to measure NTBI also in human plasma.