Activation of gut metabolite ACSL4/LPCAT3 by microplastics in drinking water mediates ferroptosis via gut-kidney axis

The environmental pollutant Benzo[a]pyrene (BaP) is commonly found in the environment, with microplastics (MPs) acting as the primary carriers of BaP into living organisms, increasing its availability in the body. However, the specific pathways and mechanisms through which MPs carrying pollutants cause kidney damage are not fully understood. This study aimed to investigate the routes and mechanisms of kidney injury in mice to low concentrations of both MPs and BaP. The combination of polystyrene (PS) and BaP disrupted lipid metabolism in the kidneys, leading to a form of cell death known as ferroptosis. However, this effect was not observed in HK-2 cells in vitro, indicating a cell-specific response. Interestingly, in HIEC-6 cells, both PS and BaP directly induced ferroptosis. These findings confirm that exposure to both PS and BaP can disrupt metabolic homeostasis in the kidneys, contributing to kidney dysfunction and cell death.