[en] The wide scale use of metal oxide nanopartic1es (NP) in the world consumer market has resulted in increase in likelihood of exposure to human beings. The potential toxic effects of these NP on mammal cells have been extensively studied. However, studies regarding neurotoxicity and specific effects on neuronal systems are very scarce. Therefore, the aim of this thesis was assessing Ihe toxic potential of titanium dioxide NP (TiO,-NP), zinc oxide NP (ZnONP) and silica-coated iron oxide NP (S-ION) on human SH-SY5Y neuronal cells, to elucidate the possible mechanism of tbeir adverse effects at tbe cellular and molecular level on the nervous system. Afier NP characterization, a battery of assays was performed to evaluate tbe viability, cytotoxicity, genotoxicity and oxidative damage in NP-exposed SH-SY5Y cells. Obtai,n ed results showed that internalisation potential of each NP was different: TiO,-NP and ION were effectively internalized in a concentration- and time-dependent manner; nevertheless, ZnO-NP were unable lo be internalized by cells. The NP potential to induce toxic effects was material-dependent: TiO,-NP did not reduce tbe viability; ION presented in general low cytotoxicity, whereas ZnO-NP affected the cells most at the cytotoxicity leve!. Similar to cytotoxicity, genotoxicity-inducing potential of metal oxide NP was found to be different for each NP. Furthermore, toxicity was found to be mediated by oxidative stress in ZnO-NP and SION exposed cells, but TiO,-NP did not induce such oxidation-related changes. The results obtained in this work contributed to increase the knowledge on tbe genotoxic and cytotoxic potential of metal oxide NP in general, and specifically on human neuronal cells.

[gl] o uso a gran escala das nanopartículas de óxidos metálicos (NP) no mercado de consumo mundial estendeuse notablemente, dando lugar a un incremento na probabilidade de exposición ás ,mesmas nos seres humanos. Os potenciais efectos tóxicos destas NP nas células de mamíferos foron ampliamente estudados. Con todo, os estudos sobre neurotoxicidade, e os efectos específicos no tecido nervoso son moi escasos. Polo tanto, o obxectivo desta tese ten sido avaliar o potencial tóxico de NP de dióxido de titanio (Ti02), óxido de zinc (ZnO) e óxido de ferro recubertas de sílice (S-ION) en células neuronais humanas SH-SY5Y, para clilucidar o posible mecanismo dos seus efectos adversos a nivel celular e molecular, no tecido nervioso humano. Lago da caracterización das NP, realizouse unha batería de ensaios para avaliar a viabilidade, citotoxicidade, xenotoxicidade e dano oxidativo nas células SH-SY5Y expostas ás NP. Os resultados obtidos mostraron que o potencial de intemalización de todos os NP é diferente; así as NP de Ti02 e as S-foron eficazmente intemalizadas, senda esta captación dependente da concentración e do tempo de exposición. Doutra banda, as NP de ZnO foron incapaces de ser intemalizadas palas células neuronais. O potencial das NP analizadas para inducir efectos tóxicos foi dependente do tipo de material. As NP de Ti02 non reduciron a viabilidade, e as S-ION presentaron en xeral baixa citotoxicidade, mentres que as NP de ZnO mostraron un alto nivel de citotoxicidade. Do mesmo xeito que no caso da citotoxicidade, o potencial xenotóxico inducido polas NP de óxidos metálicos resultou diferente para cada unha de elas. Ademais, a toxicidade atopada en células expostas a NP-ZnO e a S-ION estivo mediada por estrés oxidativo; sen embargo, para as NP-Ti02 tales cambios non se realacionaron coa oxidación. Os resultados obtidos neste traballo contribúen en xeral, a aumentar o coñecemento sobre o potencial xenotóxico e citotóxico das NP de óxidos metálicos, específicamente sobre as células neuronais humanas.