Polypropylene microplastics orchestrate oxidative stress microenvironment and trigger metabolic reprogramming in...

The high metabolism and homeostatic roles of kidney make it susceptible to microplastics (MPs); however, the specific antioxidant targets and resulting metabolic alterations remain largely unknown. In this study, the effects of polypropylene-MPs on oxidative homeostasis were refined by discriminating protein families and renal metabolic landscapes via Raman spectra and untargeted metabolomics. Polypropylene-MPs caused remarkable fluctuations in biochemical process, renal function and redox homeostasis exerting differential disturbances on expression of antioxidant genes such as Gpx5. Molecular docking results proposed the possible disruptions of polypropylene-MPs on protein structures of Gsta5, Gstt4, Gpx5 and Txnrd2. Additionally, polypropylene-MPs induced renal lesions and fibrosis, and mitochondrial cristae disorganization. A multilayer perceptron neural network illustrated the associations between key Raman spectral fingerprints (668, 1112 and 1300 cm^-1) and the renal glomerular changes. Untargeted metabolomics confirmed myriad alterations in cellular metabolic processes manifesting detoxification overload reflected by sulfated metabolites and glutathione conjugates, phospholipid remodeling, mitochondrial energy crisis, and nutritional exhaustion. These metabolic reprogramming and reactive oxygen species imbalance were intimately correlated from Raman spectral fingerprints. Our findings provided theoretical clues on the disturbance of polypropylene-MPs on oxidative homeostasis by interacting with certain antioxidant enzymes, and the consequent renal metabolic reprogramming and renal dysfunctions.