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

Sailendra Nath Sarma, Ammar Saleem, Jin Yong Lee, Maki Tokumoto, Gi Wook Hwang, Hing Man Chan, Masahiko Satoh

研究成果: Article

8 引用 (Scopus)

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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.

元の言語English
ページ(範囲)89-100
ページ数12
ジャーナルJournal of Toxicological Sciences
43
発行部数2
DOI
出版物ステータスPublished - 2018 1 1

ASJC Scopus subject areas

  • Toxicology

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    Sarma, S. N., Saleem, A., Lee, J. Y., Tokumoto, M., Hwang, G. W., Chan, H. M., & Satoh, M. (2018). Effects of long-term cadmium exposure on urinary metabolite profiles in mice. Journal of Toxicological Sciences, 43(2), 89-100. https://doi.org/10.2131/jts.43.89