Comparative evaluation of nephrotoxicity and management by macrophages of intravenous pharmaceutical iron formulations

James Connor, Xuesheng Zhang, Anne M. Nixon, Becky Webb, Joseph R. Perno

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: There is a significant clinical need for effective treatment of iron deficiency. A number of compounds that can be administered intravenously have been developed. This study examines how the compounds are handled by macrophages and their relative potential to provoke oxidative stress. Methods: Human kidney (HK-2) cells, rat peritoneal macrophages and renal cortical homogenates were exposed to pharmaceutical iron preparations. Analyses were performed for indices of oxidative stress and cell integrity. In addition, in macrophages, iron uptake and release and cytokine secretion was monitored. Results: HK-2 cell viability was decreased by iron isomaltoside and ferumoxytol and all compounds induced lipid peroxidation. In the renal cortical homogenates, lipid peroxidation occurred at lowest concentrations with ferric carboxymaltose, iron dextran, iron sucrose and sodium ferric gluconate. In the macrophages, iron sucrose caused loss of cell viability. Iron uptake was highest for ferumoxytol and iron isomaltoside and lowest for iron sucrose and sodium ferric gluconate. Iron was released as secretion of ferritin or as ferrous iron via ferroportin. The latter was blocked by hepcidin. Exposure to ferric carboxymaltose and iron dextran resulted in release of tumor necrosis factor α. Conclusions: Exposure to iron compounds increased cell stress but was tissue and dose dependent. There was a clear difference in the handling of iron from the different compounds by macrophages that suggests in vivo responses may differ.

Original languageEnglish (US)
Article numbere0125272
JournalPloS one
Volume10
Issue number5
DOIs
StatePublished - May 14 2015

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nephrotoxicity
Drug Compounding
Macrophages
macrophages
Iron
saccharated ferric oxide
iron
drugs
Pharmaceutical Preparations
Iron Compounds
Ferrosoferric Oxide
Oxidative stress
Dextrans
Kidney
Lipid Peroxidation
Cell Survival
Oxidative Stress
kidneys
dextran
sucrose

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Connor, James ; Zhang, Xuesheng ; Nixon, Anne M. ; Webb, Becky ; Perno, Joseph R. / Comparative evaluation of nephrotoxicity and management by macrophages of intravenous pharmaceutical iron formulations. In: PloS one. 2015 ; Vol. 10, No. 5.
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Comparative evaluation of nephrotoxicity and management by macrophages of intravenous pharmaceutical iron formulations. / Connor, James; Zhang, Xuesheng; Nixon, Anne M.; Webb, Becky; Perno, Joseph R.

In: PloS one, Vol. 10, No. 5, e0125272, 14.05.2015.

Research output: Contribution to journalArticle

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