Polystyrene microplastics and nanoplastics induced damage effects and metabolic abnormalities in the kidney of C57BL/6j mouse

Microplastics (MPs) and nanoplastics (NPs) in the environment present a potential threat to human health. The kidney, a vital metabolic and excretory organ, has limited regenerative capacity. However, the nephrotoxicity associated with exposure to MPs or NPs remains unclear and requires further investigation. The objective of this study was to investigate the toxic effects of environmentally relevant doses (2 μg·mL−1 and 40 μg·mL−1) of polystyrene MPs and NPs in the kidneys of adult male C57BL/6j mice. The results indicated that there were no significant changes in body weight and water intake after exposure to polystyrene MPs or NPs, but both the renal organ coefficient and renal function decreased significantly, particularly at the higher exposure dose (40 μg·mL−1). Meanwhile, exposure to polystyrene MPs and NPs caused damage to the glomerular and renal tubular of mice, along with inflammatory cell infiltration. Targeted metabolomics analysis showed that 40 μg·mL−1 of polystyrene NPs induced disorders in the TCA cycle and urea metabolism in the kidney, leading to a significant reduction in fumaric acid, malic acid, and argininosuccinate. However, 2 μg·mL−1 of polystyrene NPs resulted in an increase in the levels of lysine and glutamine. Similarly, an increase in these two metabolites were found in the kidney after exposure to 40 μg·mL−1 of polystyrene MPs. Moreover, the levels of choline, taurine, creatine, and epinephrine were also elevated. Furthermore, 2 μg·mL−1 of polystyrene MPs significantly increased serine and citric acid levels in the kidney. Considering the essential role of lipidome in kidney structure and function, we further performed untargeted lipidomics analysis to explore its changes. It was found that exposure to both 2 μg·mL−1 polystyrene MPs and 40 μg·mL−1 polystyrene NPs caused abnormal glycerolipid, glycerophospholipid, and sphingolipid metabolism in the kidney. Following exposure, an upregulation of triglycerides and a down-regulation of phosphatidylcholines, phosphatidylethanolamines, and phosphatidylinositols as well as a small amount of sphingomyelins and hexosylceramides were observed. These findings suggest that the metabolic abnormalities in the kidney are closely related to the size and exposure dosage of polystyrene particles. The structural modifications in renal tissue, functional impairment and metabolic disorders elicited by exposure to environmentally relevant doses of polystyrene MPs and NPs may significantly contribute to the occurrence and development of kidney diseases.