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Decreased dissolution of ZnO by iron doping yields nanoparticles with reduced toxicity in the rodent lung and zebrafish embryos.

Authors
Xia-T; Zhao-Y; Sager-T; George-S; Pokhrel-S; Li-N; Schoenfeld-D; Meng-H; Lin-S; Wang-X; Wang-M; Ji-Z; Zink-JI; Madler-L; Castranova-V; Lin-S; Nel-AE
Source
ACS Nano 2011 Jan; 5(2):1223-1235
NIOSHTIC No.
20038504
Abstract
We have recently shown that the dissolution of ZnO nanoparticles and Zn2 shedding leads to a series of sublethal and lethal toxicological responses at the cellular level that can be alleviated by iron doping. Iron doping changes the particle matrix and slows the rate of particle dissolution. To determine whether iron doping of ZnO also leads to lesser toxic effects in vivo, toxicity studies were performed in rodent and zebrafish models. First, we synthesized a fresh batch of ZnO nanoparticles doped with 1-10 wt % of Fe. These particles were extensively characterized to confirm their doping status, reduced rate of dissolution in an exposure medium, and reduced toxicity in a cellular screen. Subsequent studies compared the effects of undoped to doped particles in the rat lung, mouse lung, and the zebrafish embryo. The zebrafish studies looked at embryo hatching and mortality rates as well as the generation of morphological defects, while the endpoints in the rodent lung included an assessment of inflammatory cell infiltrates, LDH release, and cytokine levels in the bronchoalveolar lavage fluid. Iron doping, similar to the effect of the metal chelator, DTPA, interfered in the inhibitory effects of Zn2 on zebrafish hatching. In the oropharyngeal aspiration model in the mouse, iron doping was associated with decreased polymorphonuclear cell counts and IL-6 mRNA production. Doped particles also elicited decreased heme oxygenase 1 expression in the murine lung. In the intratracheal instillation studies in the rat, Fe doping was associated with decreased polymorphonuclear cell counts, LDH, and albumin levels. All considered, the above data show that Fe doping is a possible safe design strategy for preventing ZnO toxicity in animals and the environment.
Keywords
Cell-biology; Cell-cultures; Cellular-reactions; Cellular-uptake; Cytotoxic-effects; Injury-prevention; In-vitro-studies; Laboratory-testing; Lung-cells; Lung-function; Lung-irritants; Lung-tissue; Molecular-structure; Nanotechnology; Particulates; Particulate-sampling-methods; Pulmonary-system; Respiratory-irritants; Toxic-effects; Toxicology; Toxins; Author Keywords: ZnO; dissolution; pulmonary toxicity; iron doping; zebrafish; embryo; mouse; rat
Contact
Andre E. Nel, Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, California 90095, USA
CODEN
ANCAC3
CAS No.
7439-89-6
Publication Date
20110120
Document Type
Journal Article
Email Address
anel@mednet.ucla.edu
Fiscal Year
2011
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
1936-0851
NIOSH Division
HELD
Source Name
ACS Nano
State
CA; WV
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