Metabolic profiling of the nephrotoxicity of realgar nanoparticles in rats

The effect of realgar nanoparticles (NPs) on endogenous small molecules in rat kidney was analyzed by mass spectrometry-based metabolomics. The relationship between the changes of metabolites and the nephrotoxicity of realgar NPs was also discussed to provide a basis for the further toxicity study and the clinical application of realgar NPs. SD rats were randomly divided into seven groups, including control group, three doses (40, 200, 1 000 mg/kg) of relegar and realgar NPs groups, respectly. After 28 days of continuous intragastric administration, all rats were sacrificed and their serum and kidney samples were collected. The toxic effect of realgar NPs on kidney tissues were examined by biochemical analysis and histopathologic examination, which revealed a dose dependent nephrotoxicity induced by realgar NPs. The LC-MS and GC-MS analysis were performed for the subsequent metabolomics study. A series of 32 metabolites were found to be altered significantly in the kindey of real gar NPs treated rats, and might serve as potential nephrotoxicity biomarkers. The results of metabolic pathway analysis indicated that the nephrotoxicity of realgar NPs might be associated with the disorders of the amino acids and phosphatidic acid metabolism.