Analysis of zinc oxide nanoparticles binding proteins in rat blood and brain homogenate

Abstract

Nanoparticles (NPs) are currently used in chemical, cosmetic, pharmaceutical, and electronic products. Nevertheless, limited safety information is available for many NPs, especially in terms of their interactions with various binding proteins, leading to potential toxic effects. Zinc oxide (ZnO) NPs are included in the formulation of new products, such as adhesives, batteries, ceramics, cosmetics, cement, glass, ointments, paints, pigments, and supplementary foods, resulting in increased human exposures to ZnO. Hence, we investigated the potential ZnO nanotoxic pathways by analyzing the adsorbed proteins, called protein corona, from blood and brain from four ZnO NPs, ZnO SM20(−) , ZnO SM20(+) , ZnO AE100(−) , and ZnO AE100(+) , in order to understand their potential mechanisms in vivo. Through this study, liquid chromatography–mass spectroscopy/mass spectroscopy technology was employed to identify all bound proteins. Totals of 52 and 58 plasma proteins were identified as being bound to ZnO SM20(−) and ZnO SM20(+) , respectively. For ZnO AE100(−) and ZnO AE100(+) , 58 and 44 proteins were bound, respectively. Similar numbers of proteins were adsorbed onto ZnO irrespective of size or surface charge of the nanoparticle. These proteins were further analyzed with ClueGO, a Cytoscape plugin, which provided gene ontology and the biological interaction processes of identified proteins. Interactions between diverse proteins and ZnO nanoparticles could result in an alteration of their functions, conformation, and clearance, eventually affecting many biological processes.

Exposure to Zinc Oxide Nanoparticles Induces Neurotoxicity and Proinflammatory Response: Amelioration by Hesperidin

“…Recently, there have been reports that NPs can reach the brain via blood-brain barrier (BBB) penetration and subsequently cause damage by the induction of oxidative stress, inflammatory responses, and cytotoxicity [1][2][3][4]. It has also been found that ZnONPs could reach the brain after oral administration in animals or translocation along the olfactory nerve pathway [5,6] and may induce the changes in the spatial learning and memory ability of rats by altering the synaptic plasticity [7], and induce toxic effects in the blood and brain [8]. Earlier, ZnONPs have shown toxicity in mice brain tumor cell lines (Neuro-2a) when compared with similar sized particles of Al 2 O 3 , TiO 2 , Fe 3 O 4 , and CrO 3 [9].…”

Neurotoxicity induced by zinc oxide nanoparticles: age-related differences and interaction

“…In recent years, more and more researches have provided evidence that NPs can reach the brain via blood-brain barrier (BBB) penetration or translocation along the olfactory nerve pathway and subsequently cause damage by the induction of oxidative stress, inflammatory responses, and cytotoxicity 12 . It has also been found that ZnO NPs could reach the brain after oral and inhalatrory administration in animals 13 14 , induce the changes in the spatial learning and memory ability of rats by altering the synaptic plasticity 15 , and interact diversely with plasma and brain proteins during inducing their toxic effects in the blood and brain 16 . In vitro studies, ZnO NPs showed the strongest toxicity for mice brain tumor cell lines (Neuro-2a) when compared with similar sized particles of Al 2 O 3 , TiO 2 , Fe 3 O 4 and CrO 3 17 , decreased the activity of mice neural stem cells and human SHSY5Y neuronal cells by inducing DNA damage and cell apoptosis 18 19 , and induced apoptosis in primary cultured astrocytes through JNK signaling pathway 20 .…”

Size, Surface Properties, and Ion Release of Zinc Oxide Nanoparticles: Effects on Cytotoxicity, Dopaminergic Gene Expression, and Acetylcholinesterase Inhibition in Neuronal PC-12 Cells

“…The mitochondrial membrane potential is vital in regulating the electron transport chain and ATP generation. Also, studies have shown that ZnO NPs are predominantly bound tightly to ATP synthase in the brain, causing a mitochondria malfunction and hindering ATP production [33]. Changes in mitochondrial membrane potential have been linked to neurological disorders such as Alzheimer's disease, Parkinson's disease, and Huntington's [34].…”