Analysis of cytotoxicity and genotoxicity in a short-term dependent manner induced by a new titanium dioxide nanoparticle in murine fibroblast cells

Abstract

The extensive use of titanium dioxide nanoparticles (TiO₂ NPs) in cosmetics, food, personal care products, and industries brought concerns about their possible harmful effects. Nowadays it has become important to assess TiO₂ NPs toxic effects as a way to understand their primary risks. In the cellular environment, after cell uptake, TiO₂ NPs were described to induce reactive oxygen species (ROS) production, unbalance oxidative state, and activate apoptosis in several cell lines. Therefore, we aimed to evaluate the cytotoxicity and genotoxicity of a new TiO₂ NP surface-functionalized with sodium carboxylic ligands in a murine fibroblast cell line (LA-9). TEM and DLS analyses were performed to define nanoparticle physicochemical characteristics. We evaluated the metabolic activity and LDH released after 24 h exposition to determine cytotoxic effects. Also, we evaluated DNA damage, intracellular reactive oxygen species (ROS) production, and apoptosis induction after 24 h exposure. The TiO₂ NP impaired the cell membrane integrity at 1000 μg/mL, induced intracellular ROS production and late apoptosis at 24 h. The genotoxic effects were observed at all conditions tested at 24 h. Indeed, in fibroblasts exposed at 100 μg/mL was observed early apoptosis cells. The intracellular ROS content was increased in a dose-dependent manner. Thus, short-term exposure to TiO₂ NP promoted cytotoxicity, genotoxicity and activated apoptosis pathways based on the potential role of oxygen species in the fibroblasts cell line.