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

Abstract

András Papp,1 Tamara Horváth,1 Nóra Igaz,2 Mohana Krishna Gopisetty,2 Mónika Kiricsi,2 Dániel Simon Berkesi,3 Gábor Kozma,3 Zoltán Kónya,3 Imola Wilhelm,4 Roland Patai,4 Tamás Ferenc Polgár,4 Tamás Bellák,5 László Tiszlavicz,6 Zsolt Razga,6 Tünde Vezér1 1Department of Public Health, Faculty of Medicine, University of Szeged, Szeged, Hungary; 2Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary; 3Department of Applied and Environmental Chemistry, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary; 4Institute of Biophysics, Biological Research Centre, Szeged, Szeged, Hungary; 5Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Szeged, Szeged, Hungary; 6Department of Pathology, Faculty of Medicine, University of Szeged, Szeged, HungaryCorrespondence: András PappDepartment of Public Health, Faculty of Medicine, University of Szeged, Dóm Tér 10, H-6720, Szeged, HungaryTel [phone]Fax [phone]Email [email protected]: Non-spherical titanium dioxide (TiO2) 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 TiO2 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, TiO2 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 TiO2 nanoparticles.Keywords: apoptosis, nanoparticles, neuro-functional changes, tissue damage, toxicity

Keywords

• apoptosis
• nanoparticles
• neuro-functional changes
• tissue damage
• toxicity