Inert polystyrene nanoplastics-induced liver injury in mice was implicated in intense oxidative stress and inflammation mediated by ferroptosis.

Polystyrene nanoplastics (PS-NPs) are emerging food safety contaminants. Ferroptosis is iron-dependent cell death, but its role in PS-NPs hepatotoxicity is unclear. Mice received tail-vein injection of PS-NPs (2-8 mg/kg). PS-NPs caused liver injury (elevated transaminases) and possible renal impairment (increased uric acid/creatinine/urea). Hepatic GSH and SOD decreased, IL-1β and TNF-α increased. Mitochondrial shrinkage and cristae loss (ferroptotic features) were observed. PS-NPs upregulated ACSL4, MDA, 4-HNE and TfR, but suppressed FTH1, FPN1, SLC7A11 and GPx4. Thus, ferroptosis mediates PS-NPs liver injury with oxidative stress and inflammation, and PS-NPs may exert multi-organ toxicity.