Effects of long-term cadmium exposure on urinary metabolite profiles in mice

• Published in: Journal of toxicological sciences 2018, Vol.43(2), pp.89-100
• Main Authors: Sarma, Sailendra Nath, Saleem, Ammar, Lee, Jin-Yong, Tokumoto, Maki, Hwang, Gi-Wook, Chan, Hing Man, Satoh, Masahiko
• Format: Article
• Language: English
• Subjects: Alanine; Amino acids; Amino Acids - metabolism; Amino Acids - urine; Animals; Arginine; Aspartic acid; Biological effects; Biomarkers; Biomarkers - metabolism; Biomarkers - urine; Biosynthesis; Cadmium; Cadmium Compounds - toxicity; Carboxymethyllysine; Cyclic AMP; Environmental Exposure - adverse effects; Environmental Pollutants - toxicity; Exposure; Female; Glutamine; Guanosine; Kidney; Kidney - drug effects; Kidney - metabolism; Kidneys; Liquid chromatography; Long-term exposure; Metabolic response; Metabolism; Metabolites; Metabolomics; Mice; Mice, Inbred Strains; Nucleotides; Peptides; Peptides - metabolism; Peptides - urine; Phenylalanine; Pollutants; Proline; Quadrupoles; Time Factors; Toxicity; tRNA Glu; Tryptophan; Uridine; Urine; Urine metabolome
• ISSN: 0388-1350; 1880-3989
• DOI: 10.2131/jts.43.89

Cadmium (Cd) is a common environmental pollutant with known toxic effects on the kidney. Urinary metabolomics is a promising approach to study mechanism by which Cd-induced nephrotoxicity. The aim of this study was to elucidate the mechanism of Cd toxicity and to develop specific biomarkers by identifying urinary metabolic changes after a long-term of Cd exposure and with the critical concentration of Cd in the kidney. Urine samples were collected from wild-type 129/Sv mice after 67 weeks of 300 ppm Cd exposure and analyzed by ultra performance liquid chromatography connected with quadrupole time of flight mass spectrometer (UPLC-QTOF-MS) based metabolomics approach. A total of 40 most differentiated metabolites (9 down-regulated and 31 up-regulated) between the control and Cd-exposed group were identified. The majority of the regulated metabolites are amino acids (glutamine, L-aspartic acid, phenylalanine, tryptophan, and D-proline) indicating that amino acid metabolism pathways are affected by long-term exposure of Cd. However, there are also some nucleotides (guanosine, guanosine monophosphate, cyclic AMP, uridine), amino acid derivatives (homoserine, N-acetyl-L-aspartate, N-acetylglutamine, acetyl-phenylalanine, carboxymethyllysine), and peptides. Results of pathway analysis showed that the arginine and proline metabolism, purine metabolism, alanine, aspartate and glutamate metabolism, and aminoacyl-tRNA biosynthesis were affected compared to the control. This study demonstrates that metabolomics is useful to elucidate the metabolic responses and biological effects induced by Cd-exposure.