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

Background Titanium dioxide nanoparticles (TiO(2)NPs) have a wide range of applications in several industrial and biomedical domains. Based on the evidence, the workers exposed to inhaled nanosized TiO(2)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 TiO(2)NPs exposure. Regarding this, the present study was conducted to analyze the local effects of TiO(2)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 TiO(2)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 TiO(2)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 TiO(2)NPs were taken up by alveolar macrophages at different time points. As the results of the SEM and ICP-MS indicated, TiO(2)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 TiO(2)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 TiO(2)particles in occupational and environmental health policy.