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 3194 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 t1⁄2 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.