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Iron-rich single walled carbon nanotubes are effective catalysts of
oxidative stress in a RAW 264.7 macrophage cell culture model:
interactions with inflammatory response and in vivo implications.
VE Kagan,
AI Potapovich, AN Osipov, D Schwegler-Berry, R Mercer, ER Kisin, V
Castranova, AA Shvedova
Dept Environmental & Occupational Health and Pharmacology
University of Pittsburgh
Pittsburgh, PA, 15260 USA
kagan@pitt.edu
Single walled carbon nanotubes (SWCNT) are new emerging materials.
Their manufacturing includes catalysis on iron particles. SWCNT
induced inflammation provides a redox milieu in which iron can
synergistically enhance damage to cells/tissue. RAW 264.7
macrophages were used to characterize the cell’s ability to respond
to iron-rich/deplete SWCNT. EPR spectroscopy found that iron-rich
(but not iron-deplete) SWCNT displayed a broad signal with g value
of 2.0 and half-width of 640G attributable to high spin Fe+3.
Co-incubation of macrophages with SWCNT resulted in their engulfment
detectable by TEM. Depletion of GSH and slightly increased number of
apoptotic cells in response to SWCNT were observed. No
intracellular production of superoxide or NO was induced by SWCNT as
evidenced by flow cytometry with DHE and DAF-2-DA, respectively. EPR
spin-trapping demonstrated that iron-rich (but not iron-deplete)
SWCNT were redox-active and converted superoxide radicals produced
by zymosan-stimulated macrophages into hydroxyl radicals.
Similarly, superoxide extracellularly generated by xanthine oxidase/xanthine
yielded hydroxyl radicals. Iron-rich SWCNT oxidized ascorbate to its
radical. These in vitro results are in line with marked inflammatory
response and early onset of fibrotic changes in the lungs of C57BL/6
mice exposed to SWCNT.
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