Combined exposure of polystyrene nanoplastics and silver nanoparticles exacerbating hepatotoxicity in zebrafish mediated by ferroptosis pathway through increased silver accumulation

Silver nanoparticles (AgNPs) are extensively utilized for their antibacterial properties, leading to their release into the environment and subsequent bioaccumulation and biomagnification within the food chain. Polystyrene nanoplastics (PSNPs), as emerging pollutants, act as carriers for contaminants and alter their transformation processes. However, the toxicological effects and underlying mechanisms associated with the coexistence of these pollutants remain largely unexplored. Herein, the hepatotoxic effects and underlying mechanisms of acute combined exposure to PSNPs and AgNPs were explored using zebrafish as a model organism. After exposed to PSNPs and AgNPs, the larvae (120 hours post-fertilization) exhibited lipid metabolism disorders, increased oxidative stress, hepatomegaly, and liver dysfunction, with these effects being more pronounced than those observed with AgNPs exposure alone. This increase in hepatic toxicity may be due to the enhanced accumulation of AgNPs under combined exposure. Mechanistic investigations revealed that co-exposure led to a significant elevation in malondialdehyde and Fe²⁺ levels, a loss of mitochondrial cristae and a decrease in membrane potential, along with the abnormal expression of ferroptosis-related genes, which are hallmark indicators of ferroptosis. Furthermore, the introduction of the ferroptosis inhibitor deferoxamine alleviated all observed hepatotoxic phenotypes, thereby confirming that PS+AgNPs co-exposure induced liver injury through the ferroptosis pathway.

Environment implication

As antibacterial agents, silver nanoparticles are prevalent in the environment and pose ecological risks. Simultaneously, polystyrene nanoplastics often serve as carriers, altering the biotoxicity of adsorbed pollutants. However, research on the toxicity of nanomaterials adsorbed by nanoplastics is scarce. This study examined the increased toxicity on zebrafish livers under co-exposure to environmentally relevant concentrations of AgNPs and no observed effect concentrations of PSNPs. It proposed a novel insight that co-exposure to PSNPs and AgNPs induced liver injury in zebrafish through ferroptosis. This study provides reference for assessing the ecological risks and toxic effects of combined exposure to microplastics and nanomaterials.