Background
Titanium dioxide nanoparticles (TiO2NPs) are widely used in the fields of industry and medicine and in various consumer products. With the increasing use of TiO2NPs, there has been an increase in the number of toxicity studies; however, studies investigating the mechanism underlying its toxicity are very rare. In this study, we evaluated the potential toxic effects of TiO2NPs exposure on the lungs as well as the development of asthma in ovalbumin (OVA)-induced mouse model of asthma. We also investigated the related toxic mechanism.
Results
TiO2NPs caused pulmonary toxicity by exacerbating the inflammatory response, indicated by an increase in the number of inflammatory cells and levels of inflammatory mediators. Exposure of mice with OVA-induced asthma to TiO2NPs led to significant increases in inflammatory mediators, cytokines, and airway hyperresponsiveness compared with non-exposed mice with asthma. This was also accompanied by an increase in inflammatory cell infiltration and mucus production in the lung tissues. TiO2NPs also decreased the expression of B-cell lymphoma 2 (Bcl2) and increased the expression of thioredoxin-interacting protein (TXNIP), phospho-apoptosis signal-regulating kinase 1, Bcl2-associated X, and cleaved-caspase 3 in the lungs of asthmatic mice compared with those of non-exposed asthmatic mice. These responses were consistent with in vitro results obtained using human airway epithelial cells. TiO2NPs treated cells exhibited an increase in the mRNA and protein expression of IL-1β, IL-6, and TNF-α with an elevation of TXNIP signaling compared to non-treated cells. Moreover, pathophysiological changes induced by TiO2NPs treatment were significantly decreased by TXNIP knockdown in the airway epithelial cells.
Conclusion
Taken together, TiO2NPs exposure induced toxicological changes in the respiratory tract and exacerbated the development of asthma via activation of the TXNIP-apoptosis pathway. These results provide insights into the mechanism underlying TiO2NPs-mediated respiratory toxicity.
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