Polystyrene nanoplastics exacerbate cadmium-induced bioenergetic impairment and oxidized phospholipid accumulation in...

The coexistence of nanoplastics and conventional heavy metals poses a serious ecological threat to marine ecosystems, yet the specific mechanisms underlying their synergistic toxicity remain unclear. This study employed a comprehensive approach, encompassing tissue cadmium quantification, biochemical assays, real-time quantitative PCR, non-targeted metabolomics, and molecular docking, to investigate the combined toxic effects of polystyrene nanoplastics (PS-NPs) and cadmium (Cd) in the thick-shelled mussels (Mytilus coruscus). The results revealed a significant carrier effect: compared to the gills, PS-NPs promoted anomalous and tissue-specific accumulation of Cd in the digestive glands; this elevated toxic load led to severe dysfunction in bioenergetic metabolism. Concurrently, despite strong compensatory activation of the Nrf2/GST detoxification axis, the cellular antioxidant capacity was substantially depleted, ultimately triggering BAX/BCL-2-mediated apoptosis and resulting in irreversible tissue damage. Crucially, metabolomic analysis highlighted severe disruption of cellular membrane structural lipids under combined exposure. Mechanistically, integrative analysis indicated that Cd-driven intense oxidative stress led to the massive accumulation of oxidized phospholipids (OxPLs). These OxPLs may not be merely metabolic by-products but candidate endogenous danger-associated molecular patterns (DAMPs) with the potential to trigger the TLR4/MyD88/TRAF6 immune-inflammatory cascade, as supported by metabolomic evidence and molecular docking predictions. The molecular mechanisms proposed in this study provide new scientific insights for the ecological risk assessment of complex multi-stressor pollution.