Antioxidants and mitochondrial/lysosomal protective agents reverse toxicity induced by titanium dioxide nanoparticles on human lymphocytes

Most of the literature has focused on titanium dioxide (TiO₂) nanoparticles (NPs) toxicity, showing the importance of oxidative stress, mitochondrial dysfunction, and cell death in TiO₂-induced toxicity. For this purpose, in the current study, we investigated the protective role of antioxidant and mitochondrial/lysosomal protective agents to minimize TiO₂ NPs-induced toxicity in human lymphocytes. Human lymphocytes were obtained from heathy individuals and treated with different concentrations (80, 160, and 320 µg/mL) of TiO₂ NPs, and then human lymphocytes preincubated with butylated hydroxytoluene (BHT), cyclosporin A (CsA), and chloroquine separately were exposed to TiO₂ NPs for 6 h. In all the above-mentioned treated groups, adverse parameters such as cytotoxicity, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), lysosomal membrane destabilization, the levels of malondialdehyde (MDA), and glutathione (GSH) were measured. The results showed that TiO₂ nanoparticles induced cytotoxicity through ROS formation, MMP collapse, lysosomal damages, depletion of GSH, and lipid peroxidation. However, BHT as an antioxidant, CsA as a mitochondrial permeability transition (MPT) pore sealing agent, and chloroquine as a lysosomotropic agent, significantly inhibited all the TiO₂ NPs-induced cellular and organelle toxicities. Thus, it seems that antioxidant and mitochondrial/lysosomal protective agents are promising preventive strategies against TiO₂ NPs-induced toxicity.