Intratracheally instilled titanium dioxide nanoparticles translocate to heart and liver and activate complement cascade in the heart of C57BL/6 mice
- DOI
- Language of the publication
- English
- Date
- 2015-05-20
- Type
- Article
- Author(s)
- Husain, Mainul
- Wu, Dongmei
- Saber, Anne T.
- Decan, Nathalie
- Jacobsen, Nicklas R.
- Williams, Andrew
- Yauk, Carole L.
- Wallin, Hakan
- Vogel, Ulla
- Halappanavar, Sabina
- Publisher
- Taylor and Francis Group
Abstract
An estimated 1% or less of nanoparticles (NPs) deposited in the lungs translocate to systemic circulation and enter other organs; however, this estimation may not be accurate given the low sensitivity of existing in vivo NP detection methods. Moreover, the biological effects of such low levels of translocation are unclear. We employed a nano-scale hyperspectral microscope to spatially observe and spectrally profile NPs in tissues and blood following pulmonary deposition in mice. In addition, we characterized effects occurring in blood, liver and heart at the mRNA and protein level following translocation from the lungs. Adult female C57BL/6 mice were exposed via intratracheal instillation to 18 or 162 µg of industrially relevant titanium dioxide nanoparticles (nano-TiO2) alongside vehicle controls. Using the nano-scale hyperspectral microscope, translocation to heart and liver was confirmed at both doses, and to blood at the highest dose, in mice analyzed 24 h post-exposure. Global gene expression profiling and ELISA analysis revealed activation of complement cascade and inflammatory processes in heart and specific activation of complement factor 3 in blood, suggesting activation of an early innate immune response essential for particle opsonisation and clearance. The liver showed a subtle response with changes in the expression of genes associated with acute phase response. This study characterizes the subtle systemic effects that occur in liver and heart tissues following pulmonary exposure and low levels of translocation of nano-TiO2 from lungs.
Plain language summary
Titanium dioxide nanoparticles (TiO2-NPs) are widely used in consumer products, increasing the potential for human exposure via the inhalation, oral or dermal routes of exposure. Upon inhalation, TiO2-NPs have been shown to accumulate in other organs distant from the lungs (non-target tissues); however, the biological/toxic effects of such non-target tissue accumulation remain unclear. The present study was undertaken to help Health Canada and the international community develop a better understanding of the potential of TiO2-NPs to induce toxicity in non-target tissues. A novel microscopic method sensitive to detecting low levels of nanoparticles in tissues as well as high-content genomics tools were employed to investigate the toxicity induced by TiO2-NPs in non-target tissues, including the blood, heart, and liver of mice exposed by direct lung instillation of TiO2-NPs. Microscopy data confirmed accumulation of traces of TiO2-NPs in blood, heart and liver; however, only the heart showed robust changes in the expression of several genes and proteins involved in normal defence mechanisms (complement activation) associated with particle clearance, and in certain cardiovascular pathologies. Some of these changes were also evident in the blood, while the liver showed a very subtle response. The results of the study provide novel scientific information related to the toxicity of TiO2-NPs, which will be used by Health Canada to better understand any health risks associated with nanomaterial exposures.
Subject
- Health,
- Health and safety