Exploring the Mechanism of Kidney Injury in Mice Induced by High-Fat Diet and Polystyrene Nanoplastics Co-Exposure Through the Kidney-Gut Axis

This research aimed to establish a murine model of kidney injury induced by a combination of high-fat diet (HFD) and polystyrene nanoplastics (PS-NPs), and explored the underlying mechanisms from the perspective of the kidney-gut axis. Our results indicated that HFD combined with PS-NPs (100 nm, 25 mg/kg/d) exposure exacerbated kidney toxicity compared to HFD, as evidenced by significant increases in kidney injury markers, such as blood urea nitrogen (BUN), creatinine (CRE), kidney injury molecule 1 (KIM-1), cystatin C (Cys-C) (<i>P</i> < 0.05). In addition, the total cholesterol (TC), triglycerides (TG), nonesterified fatty acids (NEFA), interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) levels were notably increased (<i>P</i> < 0.05), while the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were notably decreased (<i>P</i> < 0.05) after exposure to HFD combined with PS-NPs. Further investigation into the underlying mechanisms revealed that the combination of PS-NPs and HFD disrupts mouse lipid metabolism through pathways involving tryptophan metabolism and glycerophospholipid metabolism, exacerbating the disorder of gut microbiota. Our research demonstrates for the first time that exposure to PS-NPs exacerbates metabolic disorders and renal toxicity in mice fed an HFD via the kidney-gut axis.