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

Revisiting the stress paradigm for silica nanoparticles: decoupling of the anti-oxidative defense, pro-inflammatory response and cytotoxicity. Arch Toxicol. 2018 May 24;: Authors: Fritsch-Decker S, Marquardt C, Stoeger T, Diabaté S, Weiss C Abstract 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 n...
Source: Archives of Toxicology - Category: Toxicology Authors: Tags: Arch Toxicol Source Type: research