Recent studies indicate that microplastics and nanoplastics (MNPs) act as key vectors for contaminants including cadmium (Cd). However, the bioavailability induced by their interaction remains controversial. Since both MNPs and Cd primarily accumulate in the liver after ingestion by organisms, hepatotoxicity induced by coexposure to MNPs (100 mg/kg body weight (BW)), 100 nm and 1 μm polystyrene (PS), and Cd (5 mg/kg BW) was examined in this study. Single or combined exposure models were established, and gavage was performed 5 times a week for 5 weeks. We observed that polystyrene (PS) accumulated in the mice liver. In comparison to the control group, all exposure groups exhibited significantly increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, altered hepatic antioxidant enzyme activities, decreased P62 protein expression, and elevated Beclin-1 expression and LC3II/I ratios, indicating that PS alone or in combination with Cd disrupted liver structures and induced excessive autophagy and oxidative damage. Specifically, the 1 μm PS group induced significantly stronger hepatotoxic effects than the 100 nm PS group. In contrast, for 100 nm PS, although it was less toxic when administered alone, it significantly enhanced the Cd-induced liver injury. Notably, triple exposure to 100 nm PS, 1 μm PS, and Cd resulted in the most severe liver dysfunction, histopathological alterations, and activated cellular autophagy. Mechanistic investigations revealed that PS exposure alone or in combination with Cd triggered excessive autophagy and oxidative stress in hepatocytes by interfering with the PI3K/AKT/mTOR signaling pathway, thereby mediating liver injury. This study innovatively demonstrates that coexposure to different-sized PS particles and Cd can lead to complex liver injury patterns while particle size influences their combined hepatotoxicity with Cd.
Li et al. (2026) studied this question.