Date Published: 
Friday, 17 January, 2014

Antioxidants may protect against oxidative stress in iron therapy treatment, studies indicate

Professor George Bailie

Intravenous iron therapy has widespread clinical use. Previous animal experiments have compared the oxidative stress induced in internal organs by intravenous iron. In two studies, we attempted to replicate some of those findings, and then to examine whether co-administered antioxidants were protective of these effects.

In the first of these studies, groups of adult rats received 1 mg/kg of iron sucrose, iron dextran, ferric carboxymaltose, or ferumoxytol weekly for five doses (doses were chosen to mimic those used in clinical practice)1. Seven days after the last dose, samples of heart, lung, liver, and kidney were analysed for nitrotyrosine and dinitro phenyl as markers of oxidative stress. All intravenous iron products stimulated an increase in both markers. Dinitro phenyl was generally stimulated less compared with nitrotyrosine except in the iron sucrose group. Dinitro phenyl was stimulated to an equal degree except in the iron dextran group, which produced over 10-fold the values of nitrotyrosine than any other iron therapy. The data indicate that iron dextran presents the highest risk of oxidative stress to internal organs, whilst iron sucrose may be the least damaging compared with the remaining iron therapies analysed1.

We subsequently used a model of urinary bladder contractility to examine effects of antioxidants2. Adult rats were divided into three groups: group 1 received ferumoxytol or iron dextran 1 mg/kg weekly for five doses; group 2 received coenzyme Q10 plus alpha lipoic acid daily for 4 weeks, then 1 mg/kg weekly of the two iron therapies for five doses, while continuing antioxidant treatment; and half of group 3 (controls) received saline and half received the antioxidant over the same time period.  Seven days after the last iron dose, liver and heart samples were analysed for nitrotyrosine and dinitro phenyl. Contractile responses of bladder strips were determined via field stimulation, carbachol, and potassium chloride. Ferumoxytol and iron dextran were shown to cause oxidative stress to several organs, but ferumoxytol appeared to cause less stress compared with iron dextran. Antioxidants attenuated the effects of iron dextran on bladder contractility2.

These data indicate that intravenous iron therapies may evoke oxidative damage to tissues. However, antioxidants such as coenzyme Q10 and alpha lipoic acid may limit such damage and thus deserve further study.