Dietary patterns reshape organ-specific biodistribution and toxicity upon exposure to polystyrene nanoplastics: Role...

Polystyrene nanoplastics (PS-NPs) are emerging foodborne contaminants associated with multi-organ toxicity. Although dietary patterns can influence the biological effects of environmental contaminants, how they modify PS-NP biodistribution and organ injury remains unclear. Mice fed a normal diet (ND), high-fat diet (HFD), or high-fructose diet (HFrD) were orally exposed to PS-NPs (80 nm, 10 mg/kg) for 1, 4, or 8 weeks. Distinct organ-specific PS-NP distribution patterns were revealed by fluorescence imaging, characterized by greater intestinal and renal accumulation in the HFD-NP80 group and greater hepatic and renal accumulation in the HFrD-NP80 group compared with the ND-NP80 group. Moreover, these patterns were accompanied by distinct toxicological responses. HFD-NP80 showed stronger biochemical evidence of renal dysfunction, with serum creatinine 1.42 times that in ND-NP80. HFrD-NP80 exhibited stronger biochemical evidence of liver injury, with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities 2.03 and 2.46 times those in ND-NP80, respectively. Mechanistically, PS-NP exposure under HFD or HFrD conditions was associated with reactive oxygen species (ROS)-mediated intestinal senescence and barrier impairment, which were alleviated by NAC intervention. Collectively, these findings suggest that dietary patterns reshape organ-specific PS-NP biodistribution and toxicological responses and that ROS-mediated intestinal senescence serves as a convergent mechanism during PS-NP exposure.