The Antioxidant Activity of Cerium Oxide Nanoparticles is Size Dependant and Blocks Aβ1‐42‐Induced Free Radical Production and Neurotoxicity

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We have demonstrated that a single 10 nM dose of cerium oxide nanoparticles (CeONP) with an average size of 10 nm, extends the lifespan & preserves neuronal function in brain cell cultures. We hypothesize that CeONP act as regenerative free radical scavengers. Here, we investigated the antioxidant activity of CeONP using EPR. Hydroxyl radicals (.OH) were generated via Fenton's reaction. Superoxide radicals (O2.–) were generated by irradiating a solution of riboflavin and DMPO with UV rays. CeONP (10 nm) completely quenched .OH & O2.– formation. CeONP with a particle size of 7 nm were less effective than 10 nm particles. We also examined the effect of Fe‐doped ceria (6% Fe), which was less effective than CeONP. The toxic fragment of Αβ, Αβ1‐42, produces free radicals & is hypothesized to be a contributory factor in Alzheimer's pathology. When incubated with spin trap Αβ1‐42 (1mg/ml) generated a 6 line EPR spectra. Αβ1‐42–induced free radical production was completely blocked by CeONP (10 nm). We also examined the neuroprotective capacity of the 3 groups of CeONP using UV, H2O2, & Αβ1‐42 challenge. In comparison to 7 nm CeONP, cell death induced by UV & H2O2 was reduced more effectively by 10 nm CeONP, whereas Fe‐doping of CeONP abrogated antioxidant protection. Neuronal death associated with Αβ1‐42 was reduced 65% by CEONP (10 nm). Our results suggest that 1) CeONP exhibit potent antioxidant activity, which is dependent on size, composition, & particle surface area and 2) CeONP protect neurons from free radical damage & Αβ1‐42 toxicity.