High-dose intranasal application of titanium dioxide nanoparticles induces the systemic uptakes and allergic airway inflammation in asthmatic mice

Background: Titanium dioxide nanoparticles (TiO₂ NPs) have a wide range of applications in several industrial and biomedical domains. Based on the evidence, the workers exposed to inhaled nanosized TiO₂ powder are more susceptible to the risks of developing respiratory diseases. Accordingly, this issue has increasingly attracted the researchers' interest in understanding the consequences of TiO₂ NPs exposure. Regarding this, the present study was conducted to analyze the local effects of TiO₂ NPs on allergic airway inflammation and their uptake in a mouse model of ovalbumin (OVA)-induced allergic airway inflammation.

Methods: For the purpose of the study, female BALB/c mice with or without asthma were intranasally administered with TiO₂ NPs. The mice were subjected to histological assessment, lung function testing, scanning electron microscopy (SEM), inductively coupled plasma mass spectrometry (ICP-MS), and NP uptake measurement. In addition, T helper (Th) 1/Th2 cytokines were evaluated in the lung homogenate using the enzyme-linked immunosorbent assay.

Results: According to the results, the mice receiving OVA alone or OVA plus TiO₂ NPs showed eosinophilic infiltrates and mucus overproduction in the lung tissues, compared to the controls. Furthermore, a significant elevation was observed in the circulating Th2 cytokines, including interleukin (IL)-4, IL-5, and IL-13 after NP exposure. The TiO₂ NPs were taken up by alveolar macrophages at different time points. As the results of the SEM and ICP-MS indicated, TiO₂ NPs were present in most of the organs in both asthmatic and non-asthmatic mice.

Conclusion: Based on the findings of the current study, intranasally or inhalation exposure to high-dose nanosized TiO₂ particles appears to exacerbate the allergic airway inflammation and lead to systemic uptake in extrapulmonary organs. These results indicate the very important need to investigate the upper limit of intranasally or inhalation exposure to nanosized TiO₂ particles in occupational and environmental health policy.