Acute phase response following pulmonary exposure to soluble and insoluble metal oxide nanomaterials in mice

Claudia Torero Gutierrez, Charis Loizides, Iosif Hafez, Anders Brostrøm, Henrik Wolff, Józef Szarek, Trine Berthing, Alicja Mortensen, Keld Alstrup Jensen, Martin Roursgaard, Anne Thoustrup Saber, Peter Møller, George Biskos, Ulla Vogel*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

14 Citationer (Scopus)
29 Downloads (Pure)

Abstract

Background
Acute phase response (APR) is characterized by a change in concentration of different proteins, including C-reactive protein and serum amyloid A (SAA) that can be linked to both exposure to metal oxide nanomaterials and risk of cardiovascular diseases. In this study, we intratracheally exposed mice to ZnO, CuO, Al2O3, SnO2 and TiO2 and carbon black (Printex 90) nanomaterials with a wide range in phagolysosomal solubility. We subsequently assessed neutrophil numbers, protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid, Saa3 and Saa1 mRNA levels in lung and liver tissue, respectively, and SAA3 and SAA1/2 in plasma. Endpoints were analyzed 1 and 28 days after exposure, including histopathology of lung and liver tissues.

Results
All nanomaterials induced pulmonary inflammation after 1 day, and exposure to ZnO, CuO, SnO2, TiO2 and Printex 90 increased Saa3 mRNA levels in lungs and Saa1 mRNA levels in liver. Additionally, CuO, SnO2, TiO2 and Printex 90 increased plasma levels of SAA3 and SAA1/2. Acute phase response was predicted by deposited surface area for insoluble metal oxides, 1 and 28 days post-exposure.

Conclusion
Soluble and insoluble metal oxides induced dose-dependent APR with different time dependency. Neutrophil influx, Saa3 mRNA levels in lung tissue and plasma SAA3 levels correlated across all studied nanomaterials, suggesting that these endpoints can be used as biomarkers of acute phase response and cardiovascular disease risk following exposure to soluble and insoluble particles
OriginalsprogEngelsk
Artikelnummer4
TidsskriftParticle and Fibre Toxicology
Vol/bind20
Udgave nummer1
Antal sider25
ISSN1743-8977
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The authors would like to thank Michael Guldbrandsen, Eva Terrida, Noor Irmam, Yasmin Akhtar, Anne Abildtrup, Ulla Tegner, Yahia Kembouche and Aleksander Penkowski for their expert technical assistance.

Funding Information:
This work was supported by the Focused Research Effort on Chemicals in the Working Environment (FFIKA) form the Danish Government. GB also acknowledges funding by the European Regional Development Fund and the Republic of Cyprus through the Research and Innovation Foundation (Project: INFRASTRUCTURE/1216/0070).

Publisher Copyright:
© 2023, The Author(s).

Citationsformater