PuSH - Publication Server of Helmholtz Zentrum München

Fritsch-Decker, S.* ; Marquardt, C.* ; Stöger, T. ; Diabaté, S.* ; Weiss, C.*

Revisiting the stress paradigm for silica nanoparticles: Decoupling of the anti-oxidative defense, pro-inflammatory response and cytotoxicity.

Arch. Toxicol. 92, 2163-2174 (2018)
Postprint DOI PMC
Open Access Green
Engineered amorphous silica nanoparticles (nanosilica) are widely used in industry yet can induce adverse effects, which might be classified according to the oxidative stress model. However, the underlying mechanisms as well as the potential interactions of the three postulated different tiers of toxicity—i.e. oxidative-, pro-inflammatory- and cytotoxic-stress response—are poorly understood. As macrophages are primary targets of nanoparticles, we used several macrophage models, primarily murine RAW264.7 macrophages, and monitored pro-inflammatory and anti-oxidative reactions as well as cytotoxicity in response to nanosilica at max. 50 µg/mL. Special attention was given to the activation of mitogen-activated protein kinases (MAPKs) as potential regulators of the cellular stress response. Indeed, according to the oxidative stress model, also nanosilica elicits an, albeit modest, anti-oxidative response as well as pronounced pro-inflammatory reactions and cytotoxicity in macrophages. Interestingly however, these three tiers of toxicity seem to operate separately of each other for nanosilica. Specifically, impeding the anti-oxidative response by scavenging of reactive oxygen species does not prevent the pro-inflammatory and cytotoxic response. Furthermore, blocking the pro-inflammatory response by inhibition of MAPKs does not impair cell death. As hazard assessment has been guided by the prevailing assumption of a dose-dependent coupling of sequential tiers of toxicity, identification of critical physico-chemical parameters to assist the safe-by-design concept should be enabled by simply monitoring one of the toxicity read-outs. Our results indicate a more complex scenario in the case of nanosilica, which triggers independent pleiotropic effects possibly also related to different material properties and primary cellular targets.
Impact Factor
Scopus SNIP
Scopus
Cited By
Altmetric
5.728
1.620
16
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Inflammation ; Macrophage ; Mapk ; Nanoparticle ; Oxidative Stress Model ; Silica
Language english
Publication Year 2018
HGF-reported in Year 2018
ISSN (print) / ISBN 0340-5761
e-ISSN 1432-0738
Quellenangaben Volume: 92, Issue: 7, Pages: 2163-2174 Article Number: , Supplement: ,
Publisher Springer
Reviewing status Peer reviewed
POF-Topic(s) 30202 - Environmental Health
Research field(s) Lung Research
PSP Element(s) G-505000-001
Scopus ID 85047324509
PubMed ID 29799070
Erfassungsdatum 2018-06-18