In Vitro Hepatotoxic and Neurotoxic Effects of Titanium and Cerium Dioxide Nanoparticles, Arsenic and Mercury Co-Exposure

This article belongs to the Special Issue Toxicity of Nanomaterials and Legacy Contaminants: Risks to the Environment and Human Health. Considering the increasing emergence of new contaminants, such as nanomaterials, mixing with legacy contaminants, including metal(loid)s, it becomes imperative to understand the toxic profile resulting from these interactions. This work aimed at assessing and comparing the individual and combined hepatotoxic and neurotoxic potential of titanium dioxide nanoparticles (TiO2NPs 0.75-75 mg/L), cerium oxide nanoparticles (CeO2NPs 0.075-10 μg/L), arsenic (As 0.01-2.5 mg/L), and mercury (Hg 0.5-100 mg/L) on human hepatoma (HepG2) and neuroblastoma (SH-SY5Y) cells. Viability was assessed through WST-1 (24 h) and clonogenic (7 days) assays and it was affected in a dose-, time- and cell-dependent manner. Higher concentrations caused greater toxicity, while prolonged exposure caused inhibition of cell proliferation, even at low concentrations, for both cell lines. Cell cycle progression, explored by flow cytometry 24 h post-exposure, revealed that TiO2NPs, As and Hg but not CeO2NPs, changed the profiles of SH-SY5Y and HepG2 cells in a dose-dependent manner, and that the cell cycle was, overall, more affected by exposure to mixtures. Exposure to binary mixtures revealed either potentiation or antagonistic effects depending on the composition, cell type and time of exposure. These findings prove that joint toxicity of contaminants cannot be disregarded and must be further explored. This research was funded by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia in the framework of the project POCI-01-0145-FEDER-029651. This work was also financed by national funds through FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of projects UIDB/04750/2020 and LA/P/0064/2020. This work was also developed within the scope of the project CICECO- Aveiro Institute of Materials, UIDB/50011/2020, UIDP/50011/2020 & LA/P/0006/2020, financed by national funds through the FCT/MEC (PIDDAC). A.T. Reis thanks the financial support of FCT through individual Grant SFRH/BPD/122112/2016. C.B. Lopes and A.C. Estrada acknowledge their research position funded by national funds (OE), through FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19. info:eu-repo/semantics/publishedVersion