title: Assessment of the toxic potential of engineered metal oxide nanomaterials using an acellular model: citrated rat blood plasma.
abstract: Citrated Sprague-Dawley rat blood plasma was used as a biologically relevant exposure medium to assess the acellular toxic potential of two metal oxide engineered nanomaterials (ENMs), zinc oxide (nZnO), and cerium oxide (nCeO2). Plasma was incubated at 37 °C for up to 48 h with ENM concentrations ranging between 0 and 200 mg/L. The degree of ENM-induced oxidation was assessed by assaying for reactive oxygen species (ROS) levels using dichlorofluorescein (DCF), pH, ferric reducing ability of plasma (FRAP), lipase activity, malondialdehyde (MDA), and protein carbonyls (PC). Whereas previous in vitro studies showed linear-positive correlations between ENM concentration and oxidative damage, our results suggested that low concentrations were generally pro-oxidant and higher concentrations appeared antioxidant or protective, as indicated by DCF fluorescence trends. nZnO and nCeO2also affected pH in a manner dependent on concentration and elemental composition; higher nZnO concentrations maintained a more alkaline pH, while nCeO2tended to decrease pH. No other biomarkers of oxidative damage (FRAP, MDA, PC, lipase activity) showed changes at any ENM concentration or time-point tested. Differential dissolution of the two ENMs was also observed, where as much as ∼31.3% of nZnO was instantaneously dissolved to Zn2+and only negligible nCeO2was degraded. The results suggest that the direct oxidative potential of nZnO and nCeO2in citrated rat blood plasma is low, and that a physiological or immune response is needed to generate appreciable damage biomarkers. The data also highlight the need for careful consideration when selecting a model for assessing ENM toxicity.
authors: a Department of Chemistry and Biochemistry , Mount Allison University , Sackville , NB , Canada.
authors: Patrick Thomas
authors: PT
authors: Gormley
authors: b Institute of Biomaterials and Biomedical Engineering , University of Toronto , Toronto , ON , Canada.
authors: Neal Ingraham
authors: NI
authors: Callaghan
authors: a Department of Chemistry and Biochemistry , Mount Allison University , Sackville , NB , Canada.
authors: Tyson James
authors: TJ
authors: MacCormack
authors: c Institute of Biochemistry, Carleton University , Ottawa , ON , Canada.
authors: Christopher Anthony
authors: CA
authors: Dieni
mesh_terms: D000818:Animals; D002021:Buffers; D002563:Cerium / Q000097:blood / Q000633:toxicity*; D002951:Citrates / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D049329:Nanostructures / Q000633:toxicity*; D010949:Plasma / Q000187:drug effects* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077559:Sodium Citrate; D015034:Zinc Oxide / Q000097:blood / Q000633:toxicity*
chemical_list: D002021:Buffers; D002951:Citrates; D017382:Reactive Oxygen Species; D000077559:Sodium Citrate; D002563:Cerium; C030583:ceric oxide; D015034:Zinc Oxide
keywords: Blood plasma; cerium oxide; metal oxide; nanoparticles; oxidation; zinc oxide