Dietary exposure to polystyrene microplastics exacerbates liver damage in fulminant hepatic failure via ROS production and neutrophil extracellular trap formation.

With the increasing influx of microplastics (MPs) into the environment, their potential toxicity represents an increasing threat to human health. However, there is a lack of relevant research surrounding the biological toxicity associated with pre-exposure to MPs under pathological conditions. To fill this gap, we established a mouse model of fulminant hepatic failure after 14 days of pre-exposure to polystyrene (PS) MPs and investigated its biological response process under combined stimulation with lipopolysaccharide (LPS)/d-galactosamine (d-GalN) and PS-MPs. The results indicated that the stress response from exposure to PS-MPs exacerbated the death induced by LPS/d-GalN and reinforced the potential of liver damage in mice. The dominant roles of inflammation promotion, reactive oxygen species (ROS), and neutrophil extracellular traps in this process were confirmed by cellular reactive oxygen species assays and experiments on oxidative stress and inflammatory responses in the liver. Transcriptomic analysis revealed that PS-MPs exacerbated the expression levels of neutrophil extracellular traps in mice treated with LPS/d-GalN, and weakened the expression of genes involved in pathways related to peroxisome, taurine, and hypotaurine metabolism, which was further validated by reverse-transcription quantitative polymerase chain reaction. This study addresses the knowledge gap regarding the adverse effects caused by a pathological state upon exposure to MPs and provides a theoretical reference for further assessment of the underlying health risks of MPs.