Chronic effects of silver nanoparticles on kidney metabolism in mice: a metabolomic approach

The release of silver nanoparticles (AgNPs) and their potential human exposure have raised significant health concerns. Although the toxic effects of AgNPs share similarities with those of Ag ions, AgNPs may exhibit distinct biological effects due to their unique physicochemical properties. Here, we compared the nephrotoxicity of AgNPs and Ag ions in mice, focusing on silver accumulation in the kidneys, metabolic alterations, and potential impacts on renal health. Male mice were exposed to AgNPs or Ag ions for 120 days. Silver accumulation in the kidneys was quantified using inductively coupled plasma mass spectrometry, and non-targeted metabolomic analysis was performed to assess metabolic changes in renal tissues. We found that AgNPs exhibited more stable and persistent accumulation in the kidneys compared to Ag ions. AgNP exposure primarily affected nucleotide and organic acid metabolism, disrupting key energy metabolism pathways such as nicotinate and nicotinamide metabolism, glycolysis, and fatty acid biosynthesis. In contrast, Ag ion exposure predominantly influenced amino acid and bile acid metabolism, potentially triggering inflammatory responses. These findings highlight the distinct biological effects of AgNPs and Ag ions, emphasizing the need for separate consideration in long-term health risk assessments and providing a scientific basis for the safe application of silver-based nanomaterials.