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/day, 42 days) and in vitro (0.4 µg/µL, 24 h) exposure models of polystyrene nanoplastics (PS-NPs, 80 nm) in mice and human kidney cortex proximal tubule epithelial cells (HK-2 cells) were established, respectively. 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)-docosahexaenoic 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-induced nephrotoxicity and preliminarily provided potential key gene targets and effective preventive measures for PS-NPs-induced nephrotoxicity.