Assessment of the extent of oxidative stress induced by intravenous ferumoxytol, ferric carboxymaltose, iron sucrose and iron dextran in a nonclinical model

Abstract

Intravenous (i.v.) iron is associated with a risk of oxidative stress. The effects of ferumoxytol, a recently approved i.v. iron preparation, were compared with those of ferric carboxymaltose, low molecular weight iron dextran and iron sucrose in the liver, kidneys and heart of normal rats. In contrast to iron sucrose and ferric carboxymaltose, low molecular weight iron dextran and ferumoxytol caused renal and hepatic damage as demonstrated by proteinuria and increased liver enzyme levels. Higher levels of oxidative stress in these tissues were also indicated, by significantly higher levels of malondialdehyde, significantly increased antioxidant enzyme activities, and a significant reduction in the reduced to oxidized glutathione ratio. Inflammatory markers were also significantly higher with ferumoxytol and low molecular weight iron dextran rats than iron sucrose and ferric carboxymaltose. Polarographic analysis suggested that ferumoxytol contains a component with a more positive reduction potential, which may facilitate iron-catalyzed formation of reactive oxygen species and thus be responsible for the observed effects. Only low molecular weight iron dextran induced oxidative stress and inflammation in the heart.

Ferumoxytol: a silver lining in the treatment of anemia of chronic kidney disease or another dark cloud?

“…Collectively, these data suggest that because ferumoxytol is a robust and stable compound, it may not have a high potential to induce oxidative stress in the kidney 46. In contrast with the study by Johnson et al, a recent in vivo study compared 40 mg/kg of ferumoxytol with ferric carboxymaltose, low molecular weight iron dextran, and iron sucrose in rats, evaluating oxidative stress parameters in the liver, heart, and kidneys 47. Doses of intravenous iron products were administered by tail vein injection every 7 days for a total of five doses, and the animals were sacrificed 24 hours after the last intravenous iron dose.…”

Considerations and Challenges in Defining Optimal Iron Utilization in Hemodialysis

“…[61][62][63] Not surprisingly, IVI formulations have been shown to induce oxidative stress, inflammation and cellular toxicity, pro-oxidant cell signaling, tissue inflammation, cellular iron deposition, and cytotoxicity in cell culture models, animal models, and acutely in human participants [63][64][65][66][67] with more labile compounds inducing more toxicity than those with larger carbohydrate shells. 68,69 IVI has also been associated with immune dysfunction, augmentation of bacterial growth, and increased Gram-positive bacteria growth in vitro.…”

Carence martiale en réanimation : diagnostic et traitement

“…De fait, le NTBI n'apparaît que lorsque la saturation de la transferrine dépasse 85-90 % (comme dans certaines hémo-chromatoses). Durant une perfusion de fer, il existe un risque d'apparition transitoire de NTBI, mais dépendant du type de fer utilisé [41]. Ce risque pourrait même varier pour un même type de fer entre la molécule originale et les biosimilaires [42].…”