Biodistribution and oxidative stress effects of a systemically-introduced commercial ceria engineered nanomaterial

Robert A. Yokel, Rebecca L. Florence, Jason M. Unrine, Michael T. Tseng, Uschi M. Graham, Peng Wu, Eric A. Grulke, Rukhsana Sultana, Sarita S. Hardas, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

The objective was to characterize the biodistribution of nanoscale ceria from blood and its effects on oxidative stress endpoints. A commercial 5% crystalline ceria dispersion in water (average particle size ∼31±4 nm) was infused intravenously into rats (0, 50, 250 and 750 mg/kg), which were terminated 1 or 20 h later. Biodistribution in rat tissues was assessed by microscopy and ICP-AES/MS. Oxidative stress effects were assessed by protein-bound 4-hydroxy 2-trans-nonenal (HNE), protein-bound 3-nitrotyrosine (3-NT), and protein carbonyls. Evans blue (EB)-albumin and Na fluorescein (Na2F) were given intravenously as blood-brain barrier integrity markers. The initial ceria t in blood was ∼7 min. Brain EB and Na 2F increased some at 20 h. Microscopy revealed peripheral organ ceria agglomerations but little in the brain. Spleen Ce concentration was >liver >blood >brain. Reticuloendothelial tissues cleared ceria. HNE was significantly increased in the hippocampus at 20 h. Protein carbonyl and 3-NT changes were small. The nanoparticle characterizations before and after biodistribution, linked with the physiological responses, provide a foundation for evaluating the effects of engineered nanomaterial physico-chemical properties on peripheral organ distribution, brain entry and resultant toxicity.

Original languageEnglish
Pages (from-to)234-248
Number of pages15
JournalNanotoxicology
Volume3
Issue number3
DOIs
StatePublished - 2009

Bibliographical note

Funding Information:
The authors thank Jason Backus for his Ce analyses by ICP-AES and gratefully acknowledge the support of this work provided by the Office of the Vice President for Research, University of Kentucky, and US EPA STAR Grant RD-833772.

Keywords

  • Blood-brain barrier
  • Ceria
  • Neurotoxicity
  • Oxidative injury
  • Rat

ASJC Scopus subject areas

  • Biomedical Engineering
  • Toxicology

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