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The modality of cell-particle interactions drives the toxicity of nanosized CuO and TiO2 in human alveolar epithelial cells

TitleThe modality of cell-particle interactions drives the toxicity of nanosized CuO and TiO2 in human alveolar epithelial cells
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2013
AuthorsMoschini, E., Gualtieri Maurizio, Colombo M., Fascio U., Camatini M., and Mantecca P.
JournalToxicology Letters
Volume222
Pagination102-116
ISSN03784274
KeywordsA549, acetylcysteine, acute toxicity, Antioxidants, article, autophagy, bafilomycin A1, cell compartmentalization, cell death, Cell Line, cell membrane, cell stress, Cell Survival, cell ultrastructure, cell viability, chemical modification, confocal microscopy, controlled study, Copper, copper ion, copper oxide, cytochemistry, cytotoxicity test, Dissolution, endocytosis, Enzyme Inhibitors, human, human cell, Humans, interleukin 8, Interleukin-8, internalization, Lipid peroxidation, lung alveolus epithelium, lysosome, Lysosomes, Metal nanoparticles, Microscopy, Mitochondria, mitochondrion, molecular interaction, molecular mechanics, nanoparticle, Nanoparticles, Oxidants, Oxidative stress, particle size, particulate matter, phagolysosome, Physicochemical Phenomena, Pneumocytes, priority journal, Proton-Translocating ATPases, Titanium, Titanium dioxide
Abstract

Metal oxide NPs are abundantly produced in nanotech industries and are emitted in several combustion processes, suggesting the need to characterize their toxic impact on the human respiratory system. The acute toxicity and the morphological changes induced by copper oxide and titanium dioxide NPs (nCuO and nTiO2) on the human alveolar cell line A549 are here investigated. Cell viability and oxidative stress have been studied in parallel with NP internalization and cell ultrastructural modifications. TiO2 NPs were abundantly internalized by cells through the endocytic pathway, even they did not induce cell death and ultrastructural lesions. Only after 24h cells were affected by an abundant NP internalization presenting a consequent altered morphology. High cytotoxicity, oxidative stress and severe ultrastructural damages were produced by nCuO, since cell membrane and mitochondria resulted to be heavily affected, even at early exposure time. nCuO-induced toxicity has been interpreted as a consequence of both NPs reactivity and copper ions dissolution in lysosomal compartments, even the free NPs, scattered throughout all the cell compartments, might contribute to the toxicity. The antioxidant N-acetylcysteine was effective in recovering nCuO exposed cells viability and Bafilomycin A1 inhibited copper ions release in phagolysosomes and significantly rescued cells, suggesting a relevant cytotoxic mechanism relative to oxidative damages and authophagic cell death, together with NP internalization and dissolution. Our results support the previous data reporting CuO NPs are highly cytotoxic and genotoxic, and associate their toxic effects with their cell penetration and interaction with various compartments. In conclusion, the so-called "Trojan horse" mechanism and autophagy, are involved in nCuO-induced cell death, even a further research is needed to explain the events occurring at early exposure time. © 2013 Elsevier Ireland Ltd.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84882749092&doi=10.1016%2fj.toxlet.2013.07.019&partnerID=40&md5=69153ec1527e15fb7b61fa325ccdfa9b
DOI10.1016/j.toxlet.2013.07.019
Citation KeyMoschini2013102