Ferric saccharate induces oxygen radical stress and endothelial dysfunction in vivo.
BACKGROUND
Intravenous iron supplementation is used widely in haemodialysis patients. However, nontransferrin-bound iron (NTBI), which increases after intravenous supplementation of ferric saccharate, has been suggested to act as a catalytic agent in oxygen radical formation in vitro and may thus contribute to endothelial impairment in vivo.


METHODS
In 20 healthy volunteers the effect of 100 mg ferric saccharate infusion was investigated. Vascular ultrasound was used to assess endothelium-dependent vasodilatation at baseline, and 10 and 240 min after ferric saccharate infusion. Whole blood was collected to measure NTBI and in vivo radical formation was assessed by electron spin resonance. A time-control study was performed using saline infusion.


RESULTS
Infusion of ferric saccharate induces a greater than fourfold increase in NTBI, as well as a transient, significant (P < 0.01) reduction of flow-mediated dilatation 10 min after infusion of ferric saccharate, when compared with saline. The generation of superoxide in whole blood increased significantly 10 and 240 min after infusion of ferric saccharate by, respectively, 70 and 53%.


CONCLUSIONS
Iron infusion at a currently used therapeutic dose for intravenous iron supplementation leads to increased oxygen radical stress and acute endothelial dysfunction.
Rooyakkers
T M
TM
Department of Internal Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Stroes
E S G
ES
Kooistra
M P
MP
van Faassen
E E
EE
Hider
R C
RC
Rabelink
T J
TJ
Marx
J J M
JJ
D000328:Adult; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005290:Ferric Compounds / Q000009:adverse effects*; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid; D006801:Humans; D007262:Infusions, Intravenous; D007501:Iron / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012907:Smoking; D014664:Vasodilation / Q000187:drug effects
D005290:Ferric Compounds; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D007501:Iron; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid