Toxicological assays and metabolomic profiling to evaluate the effects of virgin and aged micro- and nano- polystyrene plastics in SH-SY5Y human neuroblastoma cells

In the contemporary era, named plasticene, the extensive presence of micro- and nanoplastics (MPs/NPs) in all environmental matrices constitutes a global challenge that impacts on living beings, including humans. Regardless of the route of exposure, the internalized MPs/NPs may reach the central nervous system and cause cytotoxicity. The effects of nano- and micro- polystyrene particles (n/mPS; 100 μg/mL), both in virgin (v) and home oxidized (ox) form, were assessed on the human neuroblastoma cells SH-SY5Y, treated for 24 h, using toxicological endpoints and ¹H NMR-based metabolomics. A pro-oxidant effect was shown by reactive oxygen species (ROS) overproduction, present in virgin and oxidized particles, albeit 27.6 % and 29.5 % higher in ox-nPS and ox-mPS. DNA damage, mitochondrial impairment, and lipid peroxidation were found to be directly related to particle size and oxidation state (v-nPS < ox-nPS < v-mPS < ox-mPS). The metabolic changes induced by v- and ox- n/mPS in neuroblastoma cells involved the amino acid and energy metabolism, osmoregulation, oxidative stress, and neurotransmission. Interestingly, it was highlighted the ability of SH-SY5Y cells exposed to ox-nPS to counteract more effectively oxidative damage by reshaping metabolic pathways. Overall, the combination of toxicological assays and metabolic profiling confirmed the harmful effects induced by n/mPS to SH-SY5Y cells, always enhanced by the in home-oxidized counterpart, that led to cytotoxic effects and changes in cell metabolism. Despite a variable capacity for cellular homeostasis, the results shed light on the potential risks that these ubiquitous xenobiotics pose to human health, acting also as "triggers" for neurodegenerative diseases.