Polystyrene nanoplastics potentiate cadmium-induced pyroptosis and apoptosis in primary duck hepatocytes: differential responses to N-acetylcysteine.

Introduction: Nanoplastics (NPs) can act as carriers for heavy metals, and co-exposure to NPs and co-pollutants may produce greater toxicity than single exposure. However, the combined toxicity of nanoplastics and heavy metals in poultry liver cells remains poorly understood. Methods: Primary duck embryonic hepatocytes (PDEH) were used as an Results: Co-exposure to PS-NPs and Cd potentiated cadmium-induced pyroptosis-associated morphological changes, including cell swelling, rounding, membrane blebbing, and surface pore formation. Mechanistically, co-exposure activated the NLRP3/Caspase-1/GSDMD signaling axis, as indicated by increased NLRP3, cleaved Caspase-1 (P20/P10), GSDMD-NT, and intracellular IL-1β maturation. Co-exposure also exacerbated apoptosis-associated changes, including an increased Bax/Bcl-2 ratio and a higher Annexin V-positive cell population. NAC effectively reversed the apoptosis-associated endpoints but did not significantly alter the selected pyroptosis-associated markers under the present Discussion: These findings suggest that PS-NPs potentiate Cd-induced hepatotoxicity in primary duck hepatocytes, with concurrent activation of pyroptosis- and apoptosis-associated signaling. The differential responses to NAC indicate that antioxidant intervention may preferentially attenuate apoptosis-associated injury under the present