title: Rat brain pro-oxidant effects of peripherally administered 5 nm ceria 30 days after exposure.
abstract: The objective of this study was to determine the residual pro-or anti-oxidant effects in rat brain 30 days after systemic administration of a 5 nm citrate-stabilized ceria dispersion. A ∼4% aqueous ceria dispersion was iv-infused (0 or 85 mg/kg) into rats which were terminated 30 days later. Ceria concentration, localization, and chemical speciation in the brain was assessed by inductively coupled plasma mass spectrometry (ICP-MS), light and electron microscopy (EM), and electron energy loss spectroscopy (EELS), respectively. Pro- or anti-oxidant effects were evaluated by measuring levels of protein carbonyls (PC), 3-nitrotyrosine (3NT), and protein-bound-4-hydroxy-2-trans-nonenal (HNE) in the hippocampus, cortex, and cerebellum. Glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase levels and activity were measured in addition to levels of inducible nitric oxide (iNOS), and heat shock protein-70 (Hsp70). The blood brain barrier (BBB) was visibly intact and no ceria was seen in the brain cells. Ceria elevated PC and Hsp70 levels in hippocampus and cerebellum, while 3NT and iNOS levels were elevated in the cortex. Whereas glutathione peroxidase and catalase activity were decreased in the hippocampus, GR levels were decreased in the cortex, and GPx and catalase levels were decreased in the cerebellum. The GSH:GSSG ratio, an index of cellular redox status, was decreased in the hippocampus and cerebellum. The results are in accordance with the observation that this nanoscale material remains in this mammal model up to 30 days after its administration and the hypothesis that it exerts pro-oxidant effects on the brain without crossing the BBB. These results have important implications on the potential use of ceria ENM as therapeutic agents.
authors: Department of Chemistry, University of Kentucky, Lexington, KY 40506-0055, USA. Sarita.Hardas@uky.edu
authors: Sarita S
authors: SS
authors: Hardas
authors: Rukhsana
authors: R
authors: Sultana
authors: Govind
authors: G
authors: Warrier
authors: Mo
authors: M
authors: Dan
authors: Rebecca L
authors: RL
authors: Florence
authors: Peng
authors: P
authors: Wu
authors: Eric A
authors: EA
authors: Grulke
authors: Michael T
authors: MT
authors: Tseng
authors: Jason M
authors: JM
authors: Unrine
authors: Uschi M
authors: UM
authors: Graham
authors: Robert A
authors: RA
authors: Yokel
authors: D Allan
authors: DA
authors: Butterfield
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002563:Cerium / Q000008:administration & dosage* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D008854:Microscopy, Electron; D049329:Nanostructures / Q000633:toxicity*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D046590:Spectroscopy, Electron Energy-Loss; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000447:Aldehydes; D000975:Antioxidants; D018840:HSP70 Heat-Shock Proteins; C462359:tert-4-hydroxy-2-nonenal; D002563:Cerium; C002744:3-nitrotyrosine; D014443:Tyrosine; C030583:ceric oxide; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D005980:Glutathione Reductase