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

• Published in: International journal of molecular sciences 2022-03, Vol.23 (5), p.2737
• Main Authors: Rosário, Fernanda, Costa, Carla, Lopes, Cláudia B, Estrada, Ana C, Tavares, Daniela S, Pereira, Eduarda, Teixeira, João Paulo, Reis, Ana Teresa
• Format: Article
• Language: English
• Subjects: Adsorption; Apoptosis; Arsenic; Arsenic - toxicity; Binary mixtures; Bioaccumulation; Cell cycle; Cell lines; Cell proliferation; Cerium - toxicity; Contaminants; Contamination; Cytotoxicity; Exposure; Flow cytometry; Hepatoma; Humans; Liver cancer; Low concentrations; Mercury - toxicity; Metals; Nanomaterials; Nanoparticles; Nanoparticles - toxicity; Nanotechnology; Neurotoxicity; Neurotoxicity Syndromes; Photocatalysis; Titanium; Titanium - toxicity; Titanium dioxide
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23052737

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 (TiO NPs 0.75-75 mg/L), cerium oxide nanoparticles (CeO NPs 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 TiO NPs, As and Hg but not CeO NPs, 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.