TY - JOUR
T1 - Nanomaterials induce different levels of oxidative stress, depending on the used model system
T2 - Comparison of in vitro and in vivo effects
AU - Karkossa, Isabel
AU - Bannuscher, Anne
AU - Hellack, Bryan
AU - Wohlleben, Wendel
AU - Laloy, Julie
AU - Stan, Miruna S.
AU - Dinischiotu, Anca
AU - Wiemann, Martin
AU - Luch, Andreas
AU - Haase, Andrea
AU - von Bergen, Martin
AU - Schubert, Kristin
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/12/20
Y1 - 2021/12/20
N2 - The immense diversity and constant development of nanomaterials (NMs) increase the need for a facilitated risk assessment, which requires knowledge of the modes of action (MoAs) of NMs. This necessitates a comprehensive data basis, which can be obtained using omics. Furthermore, the establishment of suitable in vitro test systems is essential to follow the 3R concept and to cope with the high number of NMs. In the present study, we aimed to compare NM effects in vitro and in vivo using a multi-omics approach. We applied an integrated data analysis strategy based on proteomics and metabolomics to four silica NMs and one titanium dioxide-based NM. For the in vitro investigations, rat alveolar epithelial cells (RLE-6TN) and rat alveolar macrophages (NR8383) were treated with different doses of NMs, and the results were compared with the effects on rat lungs after short-term inhalations and instillations. Since reactive oxygen species (ROS) production has been described as a critical biological effect of NMs, we focused on different levels of oxidative stress. Thus, we found opposite changes in proteins and metabolites related to the production of reduced glutathione in alveolar epithelial cells and alveolar macrophages, demonstrating that the MoAs of NMs depend on the model system used. Interestingly, in vivo, pathways related to inflammation were more affected than oxidative stress responses. Hence, the assignment of the observed effects to levels of oxidative stress was also different in vitro and in vivo. However, the overall classification of “active” and “passive” NMs was consistent in vitro and in vivo, suggesting that both cell lines tested are suitable for the assessment of NM toxicity. In summary, the results presented here highlight the need to carefully review model systems to decipher the extent to which they can replace in vivo assays.
AB - The immense diversity and constant development of nanomaterials (NMs) increase the need for a facilitated risk assessment, which requires knowledge of the modes of action (MoAs) of NMs. This necessitates a comprehensive data basis, which can be obtained using omics. Furthermore, the establishment of suitable in vitro test systems is essential to follow the 3R concept and to cope with the high number of NMs. In the present study, we aimed to compare NM effects in vitro and in vivo using a multi-omics approach. We applied an integrated data analysis strategy based on proteomics and metabolomics to four silica NMs and one titanium dioxide-based NM. For the in vitro investigations, rat alveolar epithelial cells (RLE-6TN) and rat alveolar macrophages (NR8383) were treated with different doses of NMs, and the results were compared with the effects on rat lungs after short-term inhalations and instillations. Since reactive oxygen species (ROS) production has been described as a critical biological effect of NMs, we focused on different levels of oxidative stress. Thus, we found opposite changes in proteins and metabolites related to the production of reduced glutathione in alveolar epithelial cells and alveolar macrophages, demonstrating that the MoAs of NMs depend on the model system used. Interestingly, in vivo, pathways related to inflammation were more affected than oxidative stress responses. Hence, the assignment of the observed effects to levels of oxidative stress was also different in vitro and in vivo. However, the overall classification of “active” and “passive” NMs was consistent in vitro and in vivo, suggesting that both cell lines tested are suitable for the assessment of NM toxicity. In summary, the results presented here highlight the need to carefully review model systems to decipher the extent to which they can replace in vivo assays.
KW - Alveolar epithelial cells
KW - Alveolar macrophages
KW - Instillation
KW - Mode of action
KW - Omics
KW - STIS
UR - http://www.scopus.com/inward/record.url?scp=85113275804&partnerID=8YFLogxK
U2 - 10.1016/j.scitotenv.2021.149538
DO - 10.1016/j.scitotenv.2021.149538
M3 - Article
C2 - 34428663
AN - SCOPUS:85113275804
SN - 0048-9697
VL - 801
JO - Science of the Total Environment
JF - Science of the Total Environment
M1 - 149538
ER -