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Open AccessArticle

Multi-Organ NMR Metabolomics to Assess In Vivo Overall Metabolic Impact of Cisplatin in Mice

1
Department of Chemistry and CICECO–Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal
2
LAQV/REQUIMTE, Department of Drug Sciences, Laboratory of Pharmacology, Faculty of Pharmacy, University of Porto, 4150-755 Porto, Portugal
3
“Química-Física Molecular”, University of Coimbra, 3004-535 Coimbra, Portugal
4
Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, 3000-456 Coimbra, Portugal
*
Author to whom correspondence should be addressed.
Metabolites 2019, 9(11), 279; https://doi.org/10.3390/metabo9110279
Received: 24 October 2019 / Revised: 8 November 2019 / Accepted: 11 November 2019 / Published: 13 November 2019
(This article belongs to the Special Issue Metabolomics in the Study of Disease)
This work describes, to our knowledge, the first NMR metabolomics analysis of mice kidney, liver, and breast tissue in response to cisplatin exposure, in search of early metabolic signatures of cisplatin biotoxicity. Balb/c mice were exposed to a single 3.5 mg/kg dose of cisplatin and then euthanized; organs (kidney, liver, breast tissue) were collected at 1, 12, and 48 h. Polar tissue extracts were analyzed by NMR spectroscopy, and the resulting spectra were studied by multivariate and univariate analyses. The results enabled the identification of the most significant deviant metabolite levels at each time point, and for each tissue type, and showed that the largest metabolic impact occurs for kidney, as early as 1 h post-injection. Kidney tissue showed a marked depletion in several amino acids, comprised in an overall 13-metabolites signature. The highest number of changes in all tissues was noted at 12 h, although many of those recovered to control levels at 48 h, with the exception of some persistently deviant tissue-specific metabolites, thus enabling the identification of relatively longer-term effects of cDDP. This work reports, for the first time, early (1–48 h) concomitant effects of cDDP in kidney, liver, and breast tissue metabolism, thus contributing to the understanding of multi-organ cDDP biotoxicity. View Full-Text
Keywords: cisplatin; mice; mouse model; in vivo; NMR; metabolomics; metabonomics; kidney; liver; breast tissue cisplatin; mice; mouse model; in vivo; NMR; metabolomics; metabonomics; kidney; liver; breast tissue
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Carneiro, T.J.; Araújo, R.; Vojtek, M.; Gonçalves-Monteiro, S.; Diniz, C.; Batista de Carvalho, A.L.; Marques, M.P.M.; Gil, A.M. Multi-Organ NMR Metabolomics to Assess In Vivo Overall Metabolic Impact of Cisplatin in Mice. Metabolites 2019, 9, 279.

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