Fasn involved in the nephrotoxicity induced by polystyrene nanoplastics and the intervention of melatonin through intestinal microbiota-mediated lipid metabolism disorder

Nanoplastics (NPs) can accumulate in the kidney and cause kidney injury, but the multi-organ interaction mechanism and preventive measures of kidney injury are still unclear. In this study, in vivo (60 μg/d, 42 d) and in vitro (0.4 μg/L, 24 h) exposure models of polystyrene nanoplastics (PS-NPs, 80 nm) in mice and HK-2 cells were established. Our study revealed that PS-NPs caused obvious pathological changes and impaired renal function in mice, which were related to lipid metabolism disorders mediated by intestinal flora. Desulfovibrionales-fatty acid synthase (Fasn)-eicosapentaenoic Acid (DHA) pathway may be one of the mechanisms of kidney injury in mice. Importantly, we also found that melatonin attenuates PS-NPs-induced nephrotoxicity by modulating lipid metabolism disorders (represented by DHA) and affects Fasn expression. In conclusion, our study revealed the important role of intestinal flora-mediated lipid metabolism in PS-NPs nephrotoxicity, and initially provided potential key gene targets and effective preventive measures for PS-NPs induced nephrotoxicity.