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| Status |
Public on Mar 31, 2015 |
| Title |
Intratracheally Instilled Titanium Dioxide Nanoparticles Translocate to Heart and liver and Activate Complement Cascade in the Heart of C57BL/6 Mice (Heart) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
An estimated 1% or less of the nanoparticles (NPs) deposited in lungs translocate to systemic circulation and enter other organs; however this estimation may not be accurate considering the low sensitivity of the existing in vivo NP detection methods. Moreover, the biological outcomes of such low levels of translocation are not elucidated. The objectives of the present study were to employ a Nano-scale Hyperspectral Microscope to spatially observe and spectrally profile NPs in tissues, and characterize the effects of NPs in blood, liver and heart following pulmonary deposition and subsequent translocation from lungs. Adult female C57BL/6 mice were exposed via intratracheal instillation to 18 and 162 µg per mouse of industrially relevant non-doped titanium dioxide nanoparticles (nano-TiO2). Using the Nano-scale Hyperspectral Microscope translocation to heart and liver was confirmed at both doses and to blood at the highest dose at 24 hours post-exposure time-point. The analysis of biological effects using DNA microarrays, RT-qPCR and ELISA revealed activation of complement cascade and inflammatory process in heart and specific activation of complement factor 3 in blood, potentially suggestive of activation of early innate immune response essential for particle opsonisation and clearance. The liver showed subtle response with changes in the expression of few genes associated with acute phase genes. This study establishes a direct link between particle translocation and systemic effects.
An estimated 1% or less of the nanoparticles (NPs) deposited in lungs translocate to systemic circulation and enter other organs; however this estimation may not be accurate considering the low sensitivity of the existing in vivo NP detection methods. Moreover, the biological outcomes of such low levels of translocation are not elucidated. The objectives of the present study were to employ a Nano-scale Hyperspectral Microscope to spatially observe and spectrally profile NPs in tissues, and characterize the effects of NPs in blood, liver and heart following pulmonary deposition and subsequent translocation from lungs. Adult female C57BL/6 mice were exposed via intratracheal instillation to 18 and 162 µg per mouse of industrially relevant non-doped titanium dioxide nanoparticles (nano-TiO2). Using the Nano-scale Hyperspectral Microscope translocation to heart and liver was confirmed at both doses and to blood at the highest dose at 24 hours post-exposure time-point. The analysis of biological effects using DNA microarrays, RT-qPCR and ELISA revealed activation of complement cascade and inflammatory process in heart and specific activation of complement factor 3 in blood, potentially suggestive of activation of early innate immune response essential for particle opsonisation and clearance. The liver showed subtle response with changes in the expression of few genes associated with acute phase genes. This study establishes a direct link between particle translocation and systemic effects.
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| Overall design |
This experiment consists of one dose of nano-TiO2 (162 ug) and one control. There are 2 time points for each treatment and control group, e.g., day 1 and day 28. Each dose or time point has 5-6 biological replicates. There are total 22 samples (arrays)
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| Contributor(s) |
Husain M, Gupta P, Wu D, Saber AT, Jacobsen NR, Williams A, Yauk C, Wallin H, Vogel U, Halappanavar S |
| Citation(s) |
25993494 |
| Submission date |
Mar 28, 2014 |
| Last update date |
Jul 03, 2019 |
| Contact name |
Mainul Husain |
| E-mail(s) |
husainm1@gmail.com
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| Phone |
613-957-3135
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| Organization name |
Health Canada
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| Street address |
50 Colombine Driveway
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| City |
Ottawa |
| ZIP/Postal code |
K2B8C8 |
| Country |
Canada |
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| Platforms (1) |
| GPL7202 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version) |
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| Samples (22)
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| Relations |
| BioProject |
PRJNA242913 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE56324_RAW.tar |
93.7 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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