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

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 similar to 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-transnonenal (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 (BBB) integrity markers. The initial ceria t(1/2) in blood was similar to 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.