Journal article
Comparative evaluation of nephrotoxicity and management by macrophages of intravenous pharmaceutical iron formulations
PloS one, v 10(5), pp e0125272-e0125272
14 May 2015
PMID: 25973894
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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.
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.
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.
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.
Metrics
8 Record Views
Details
- Title
- Comparative evaluation of nephrotoxicity and management by macrophages of intravenous pharmaceutical iron formulations
- Creators
- James R Connor - Penn State Milton S. Hershey Medical CenterXuesheng Zhang - Penn State Milton S. Hershey Medical CenterAnne M Nixon - Penn State Milton S. Hershey Medical CenterBecky Webb - Penn State Milton S. Hershey Medical CenterJoseph R Perno - Luitpold Pharmaceuticals, Inc., Norristown, Pennsylvania, United States of America
- Publication Details
- PloS one, v 10(5), pp e0125272-e0125272
- Publisher
- Public LIbrary of Science (PLOS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Health Sciences
- Web of Science ID
- WOS:000354545600014
- Scopus ID
- 2-s2.0-84929377825
- Other Identifier
- 991021866821404721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Urology & Nephrology