title: Iron oxide particles for molecular magnetic resonance imaging cause transient oxidative stress in rat macrophages.
abstract: Iron oxide particles are a promising marker in molecular magnetic resonance imaging. They are used to label distinct cell populations either in vitro or in vivo. We investigated for the first time whether small citrate-coated very small superparamagnetic iron oxide particles (VSOPs) can lead to an increase in cellular oxidative stress. We incubated rat macrophages (RAW) in vitro with iron oxide particles. We observed a massive uptake of VSOPs measured both with atomic absorption spectroscopy and with NMR, which could be visualized by confocal laser scanning microscopy. After incubation, cells were lysed and the levels of malonyldialdehyde (MDA) and protein carbonyls were determined. We found a significant increase in both MDA and protein carbonyl levels after incubation with the particles. Surprisingly, 24 h after incubation, a significant indication of oxidative stress could no longer be observed. The increase in oxidative stress seems to be transient and closely linked to the incubation procedure. The iron chelator desferal and the intracellular spin trap PBN caused a significant reduction in oxidative stress to almost control levels. This indicates that the augmentation of oxidative stress is closely linked to the free iron during incubation. Proliferation assays showed that incorporation of VSOPs did not lead to long-term cytotoxic effects even though the iron oxide particles remained in the cell. Magnetic labeling of cells with VSOPs seems to cause transient oxidative conditions not affecting cellular viability and seems to be a usable approach for molecular magnetic resonance imaging.
authors.affiliation: Department of Radiology and Neuroradiology, Berlin, Germany.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Stroh
authors.forename: Claus
authors.initials: C
authors.lastname: Zimmer
authors.forename: Cindy
authors.initials: C
authors.lastname: Gutzeit
authors.forename: Manuela
authors.initials: M
authors.lastname: Jakstadt
authors.forename: Franziska
authors.initials: F
authors.lastname: Marschinke
authors.forename: Tobias
authors.initials: T
authors.lastname: Jung
authors.forename: Herbert
authors.initials: H
authors.lastname: Pilgrimm
authors.forename: Tilman
authors.initials: T
authors.lastname: Grune
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D002244:Carbon / Q000737:chemistry; D002455:Cell Division; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D005290:Ferric Compounds / Q000737:chemistry* / Q000378:metabolism; D005609:Free Radicals; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D007502:Iron Chelating Agents / Q000494:pharmacology; D015227:Lipid Peroxidation; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D008315:Malondialdehyde / Q000494:pharmacology; D018613:Microscopy, Confocal; D018384:Oxidative Stress; D011522:Protons; D051381:Rats; D013997:Time Factors
chemical_list: D000975:Antioxidants; D005290:Ferric Compounds; D005609:Free Radicals; D007502:Iron Chelating Agents; D011522:Protons; C000499:ferric oxide; D008315:Malondialdehyde; D002244:Carbon; D007501:Iron; D003676:Deferoxamine