Maternal exposure to iron oxide nanoparticles is associated with ferroptosis in the brain: A chicken embryo model analysis

Abstract

Ferroptosis is a name coined in 2012 for cell death driven by irondependent devastating lipid peroxidation (Shen et al., 2018). It is distinct from other cell death modes, including apoptosis and necrosis, in underlying mechanism, morphology and function in normal cell life (Yang & Stockwell, 2016). Ferroptotic cells appear with round cytoplasm and the normal nuclear size and chromatin density under light microscopy (Xie et al., 2016). From a mechanism perspective (Figure 1c), ferroptosis can be induced through inhibition of glutamate/cystine antiporter (system x − c ) by compounds like erastin, glutamate and sulfasalazine. Inactivation of glutathione peroxidase 4 (GPX4), which converts lipid hydroperoxides to non-toxic lipid alcohols (Stockwell et al., 2017), by compounds like RAS-selective lethal small molecule 3 (RSL3) or depletion of cells from reduced glutathione (GSH) (Yang & Stockwell, 2016) can also trigger ferroptosis. Moreover, inhibitors of the mevalonate pathway, such as statins, can initiate ferroptosis. They can impede with isopentenylation of selenocysteine-tRNA during the

Altered Morpho-Functional Features of Neurogenesis in Zebrafish Embryos Exposed to Non-Combustion-Derived Magnetite

“…Additionally, to verify the presence of a nanosized component in the particle population, we performed an ARM analysis that highlighted the presence of a small portion of nanosized magnetite agglomerates in the sample that would have been administered to zebrafish embryos. Subsequently, in agreement with previous studies [ 27 , 39 ], we established that the exposure of fish embryos to magnetite concentrations up to 400 µg/mL does not affect embryo viability, as it does not induce morphological defects in key tissues/organs. With the great advantage of embryo transparency presented by the zebrafish model, we were able to measure in vivo the redox state within the brain of magnetite-treated fishes, confirming a dose-dependent increase in ROS levels.…”

“…In addition, in vitro studies have suggested that iron oxide nanoparticles, including magnetite, can cross the placental barrier, reaching the embryo and inevitably affecting its development [ 25 , 26 ]. One study performed in chicken revealed that maternal exposure to magnetite allowed these particles to reach the embryo, causing damaging cerebral effects [ 27 ]. Nevertheless, at the present time, no evidence has shown whether cleavage fragments detaching from coarse magnetite particles or elemental Fe released by coarse magnetite particles can affect brain cell formation processes during development.…”