Toxicological Assessment of CoO and La₂O₃Metal Oxide Nanoparticles in Human Small Airway Epithelial Cells

Abstract

Cobalt monoxide (CoO) and lanthanum oxide (La2O3) nanoparticles are 2 metal oxide nanoparticles with different redox potentials according to their semiconductor properties. By utilizing these two nanoparticles, this study sought to determine how metal oxide nanoparticle’s mode of toxicological action is related to their physio-chemical properties in human small airway epithelial cells (SAEC). We investigated cellular toxicity, production of superoxide radicals and alterations in gene expression related to oxidative stress, and cellular death at 6 and 24 h following exposure to CoO and La2O3 (administered doses: 0, 5, 25, and 50 μg/ml) nanoparticles. CoO nanoparticles induced gene expression related to oxidative stress at 6 h. After characterizing the nanoparticles, transmission electron microscope analysis showed SAEC engulfed CoO and La2O3 nanoparticles. CoO nanoparticles were toxic after 6 and 24 h of exposure to 25.0 and 50.0 μg/ml administered doses, whereas, La2O3 nanoparticles were toxic only after 24 h using the same administered doses. Based upon the Volumetric Centrifugation Method in vivo Sedimentation, Diffusion, and Dosimetry, the dose of CoO and La2O3 nanoparticles delivered at 6 and 24 h were determined to be: CoO: 1.25, 6.25, and 12.5 μg/ml; La2O3: 5, 25, and 50 μg/ml and CoO: 4, 20, and 40 μg/ml; and La2O3: 5, 25, 50 μg/ml, respectively. CoO nanoparticles produced more superoxide radicals and caused greater stimulation of total tyrosine and threonine phosphorylation at both 6 and 24 h when compared with La2O3 nanoparticles. Taken together, these data provide evidence that different toxicological modes of action were involved in CoO and La2O3 metal oxide nanoparticle-induced cellular toxicity.

Differential pulmonary effects of CoO and La2O3 metal oxide nanoparticle responses during aerosolized inhalation in mice

“…CoO nanoparticles were purchased from SkySpring Nanomaterials (Houston, TX) and La 2 O 3 nanoparticles were purchased from Nanostructured & Amorphous Materials, Inc. (Houston, TX). The physicochemical characteristics of these particles are given in Table 1 [ 3 , 7 ].…”

“…We demonstrate that there are indeed differences in the pulmonary responses to CoO and La 2 O 3 nanoparticles in the induction of acute vs. chronic pulmonary responses. Such differences are reflective of adverse outcome pathways (AOPs) for these materials [ 11 ], which we previously established by our cellular and bolus aspiration studies [ 3 , 6 , 7 ]. The results of this inhalation study support the usefulness of a tiered approach including mechanistically relevant in vitro screening tests and bolus in vivo exposures in predicting pulmonary responses during inhalation exposures to nanoparticles [ 11 ].…”

“…Previously, we investigated CoO and La 2 O 3 nanoparticle-induced cellular toxicity, production of superoxide radicals, and alterations in gene expression related to oxidative stress and cellular death in human small airway epithelial cells (SAEC) [ 7 ]. Results in that study showed that CoO nanoparticles caused more adverse effects than La 2 O 3 nanoparticles, using cytotoxicity assays in SAEC.…”

Mass spectrometry-based proteomics for system-level characterization of biological responses to engineered nanomaterials

“…Using this method, Rinna et al showed that silver ENMs activate mitogen-activated protein kinases such as ERK1/2 and JNK1/2 human epithelial embryonic cells [58]. Similarly, an increase in total tyrosine and threonine phosphorylation has been found in human small airway epithelial cells under exposure to both CoO and La 2 O 3 ENMs [59]. With the advances of MS-based proteomics, global phosphoproteome profiling now allows quantifying > 10,000 site-specific phosphorylation events in one experiment.…”

Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling in Rat Lung, Blood, and Serum for Assessment of Laser Printer-Emitted Nanoparticle Inhalation Exposure-Induced Disease Risks

“…This study will focus on a specific real-world LCPM: laser printer-emitted particles (PEPs) generated from nano-enabled toners which has been studied extensively by the authors and others over the last decade [18,19]. In US alone, 23 million printers are produced annually, and over 160,000 workers are employed in copier centers [20][21][22][23][24][25][26][27][28]. The new generation of toners contain ENPs, such as metals and metal oxides, and that PEPs with mode sizes of 49-208 nm are released during printing at concentrations of up to 1.3 million particles/cm 3 [15].…”