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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 t½ in blood was ~7 min. Brain EB and Na2F 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.
| Abbreviations | ||
| AES | = | atomic (optical) emission spectrometry |
| BBB | = | blood-brain barrier |
| Ce | = | ceria |
| EB | = | Evans blue |
| EM | = | electron microscopy |
| ENM | = | engineered nanomaterial |
| ICP | = | inductively-coupled plasma |
| MDL | = | method detection limit |
| MS | = | mass spectrometry |
| HNE | = | 4-hydroxy-2-trans-nonenal |
| 3-NT | = | 3-nitrotyrosine |
| RES | = | reticuloendothelial system |
| RNS | = | reactive nitrogen species |
| ROS | = | reactive oxygen species |
| RPD | = | relative percent difference |
| SD | = | standard deviation |
| XRD | = | X-ray diffraction |
| Abbreviations | ||
| AES | = | atomic (optical) emission spectrometry |
| BBB | = | blood-brain barrier |
| Ce | = | ceria |
| EB | = | Evans blue |
| EM | = | electron microscopy |
| ENM | = | engineered nanomaterial |
| ICP | = | inductively-coupled plasma |
| MDL | = | method detection limit |
| MS | = | mass spectrometry |
| HNE | = | 4-hydroxy-2-trans-nonenal |
| 3-NT | = | 3-nitrotyrosine |
| RES | = | reticuloendothelial system |
| RNS | = | reactive nitrogen species |
| ROS | = | reactive oxygen species |
| RPD | = | relative percent difference |
| SD | = | standard deviation |
| XRD | = | X-ray diffraction |