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J Toxicol Sci. 2018;43(2):89-100. doi: 10.2131/jts.43.89.

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

Author information

1
Department of Biology, University of Ottawa, Canada.
2
Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University.
3
Laboratory of Molecular Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University.

Abstract

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.

KEYWORDS:

Cadmium; Kidney; Long-term exposure; Urine metabolome

PMID:
29479038
DOI:
10.2131/jts.43.89
[Indexed for MEDLINE]
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