Pulmonary impact of titanium dioxide nanorods: examination of nanorod-exposed rat lungs and human alveolar cells

Abstract

Tamara Horváth,1 András Papp,1 Nóra Igaz,2 Dávid Kovács,2 Gábor Kozma,3 Vivien Trenka,2 László Tiszlavicz,4 Zsolt Rázga,4 Zoltán Kónya,3 Mónika Kiricsi,2 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; 4Department of Pathology, Faculty of Medicine, University of Szeged, Szeged, Hungary Background: Titanium dioxide nanoparticles have numerous applications, resulting in human exposure. Nonetheless, available toxicological and safety data are insufficient regarding aspherical particles, such as rod-shaped nanoparticles. Methods: In a combined in vitro–in vivo approach, cultured A549 lung alveolar adenocarcinoma cells were treated with approximately 15×65 nm TiO2 nanorod-containing medium, while young adult rats received the same substance by intratracheal instillation for 28 days in 5 and 18 mg/kg body-weight doses. Nanoparticle accumulation in the lungs and consequent oxidative stress, cell damage, and inflammation were assessed by biochemical and histopathological methods. Results: Titanium was detected in tissue samples by single-particle inductively coupled plasma mass spectrometry. Nanoparticles were visualized inside cultured A549 cells, within pulmonary macrophages, and in hilar lymph nodes of the rats. A549 cells showed dose-dependent oxidative stress and lethality, and the observed nanoparticle-laden endosomes suggested deranged lysosomal function and possible autophagy. Strongly elevated Ti levels were measured in the lungs of nanorod-treated rats and moderately elevated levels in the blood of the animals. Numerous cytokines, indicating acute and also chronic inflammation, were identified in the lung samples of TiO2-exposed rodents. Conclusion: Several signs of cell and tissue damage were detected in both the cultured alveolar cells and in treated rats’ lungs. Rod-shaped nanoparticulate TiO2 may consequently be more harmful than has generally been supposed. The occupational health risk suggested by the results calls for improved safety measures. Keywords: nanoparticles, toxicity, oxidative stress, autophagy, cytokines, inflammation

Keywords

• nanoparticles
• toxicity
• oxidative stress
• autophagy
• cytokines
• inflammation