<p>Presence of Titanium and Toxic Effects Observed in Rat Lungs, Kidneys, and Central Nervous System in vivo and in Cultured Astrocytes in vitro on Exposure by Titanium Dioxide Nanorods</p>

Abstract

Background Non-spherical titanium dioxide (TiO 2 ) nanoparticles have been increasingly applied in various biomedical and technological fields. Their toxicological characterization is, however, less complete than that of roundish nanoparticles. Materials and Methods Anatase form TiO 2 nanorods, ca. 15x65 nm in size, were applied to cultured astrocytes in vitro and to the airways of young adult Wistar rats in vivo in 5, 10, and 8 mg/kg BW dose for altogether 28 days. Presence of nanorods and cellular damage was investigated in the astrocytes and in rat lungs and kidneys. Functional damage of the nervous system was studied by electrophysiological methods. Results The treated astrocytes showed loss of viability without detectable apoptosis. In rats, TiO 2 nanorods applied to the airways reached the blood and various organs including the lungs, kidneys, and the central nervous system. In lung and kidney samples, nanorods were observed within (partly damaged) phagolysosomes and attached to organelles, and apoptotic cell death was also detected. In cortical and peripheral electrophysiological activity, alterations corresponding to energy shortage (resulting possibly from mitochondrial damage) and astrocytic dysfunction were detected. Local titanium levels and relative weight of the investigated organs, apoptotic cell death in the lungs and kidneys, and changes in the central and peripheral nervous activity were mostly proportional to the applied doses, and viability loss of the cultured astrocytes was also dose-dependent, suggesting causal relationship of treatments and effects. Conclusion Based on localization of the visualized nanorods, on neuro-functional changes, and on literature data, the toxic mechanism involved mitochondrial damage, oxidative stress, and apoptotic cell death. These indicate potential human toxicity and occupational risk in case of exposure to rod-shaped TiO 2 nanoparticles.

Neonatal Rat Glia Cultured in Physiological Normoxia for Modeling Neuropathological Conditions In Vitro

“…[ 94 , 95 ]. The neonatal glial cultures are also useful for studies on neurodegenerative diseases, including PD [ 96 , 97 ], AD [ 98 , 99 , 100 , 101 ], MS [ 102 , 103 ], or triggered by exposure to environmental toxicants and pollution [ 104 , 105 , 106 ]. Culturing cells in oxygen concentration is relevant for that present in the nervous tissue, and the elimination of serum and other supplements create opportunities to eliminate microenvironmental clues, potentially affecting investigated processes or modulating drug effectiveness.…”

TiO2 Nanoparticles and Their Effects on Eukaryotic Cells: A Double-Edged Sword

“…Several in vivo and in vitro studies have demonstrated the neurotoxicity of TiO 2 NPs through programmed cell death processes, such as apoptosis, autophagy and necroptosis depending on the duration of exposure and the dose-dependence. Although low-dose exposure could not induce any acute neurotoxicity, chronic exposure to low dose TiO 2 NPs results in TiO 2 accumulation and might lead to dramatic changes in the brain [ 43 , 46 , 47 , 48 , 49 , 50 ].…”

“…Pulmonary in vivo studies on rats support the carcinogenicity of TiO 2 NPs in intratracheal and inhalation studies [ 41 ]. Mitochondrial damage, oxidative stress, and apoptotic cell death in a dose-dependent manner were involved in the toxic mechanistic pathways [ 47 ]. Lung inflammation was associated with dose-dependent increases.…”

“…Lung inflammation was associated with dose-dependent increases. However, no clinical signs of obvious acute toxicity were observed [ 41 , 47 ]. In vitro, cell lines of human lung origin showed increased ROS generation and apoptotic death on exposure to TiO 2 NPs [ 54 ].…”

Modulatory Role of Quercetin in Mitochondrial Dysfunction in Titanium Dioxide Nanoparticle-Induced Hepatotoxicity

“…The rapid breakthrough in nanoscience research has resulted in growth in the manufacture and usage of nanoparticles, which are less than 100 nm in dimension. , Conventionally, nanoparticles of sizes ranging to as low as several nanometers are often produced as byproducts of anthropogenic activities, such as simple combustion, chemical manufacturing, welding, smelting, vehicular combustion, airplane engines, and ore refining . TiO 2 nanoparticles are widely used because of their unique properties in various biological and allied domains, such as medicine, drug delivery, transfection vectors, food industry, and fluorescent labels .…”