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

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 euthanize...

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Bibliographic Details
Published in:Metabolites 2019-11, Vol.9 (11), p.279
Main Authors: Carneiro, Tatiana J, Araújo, Rita, Vojtek, Martin, Gonçalves-Monteiro, Salomé, Diniz, Carmen, Batista de Carvalho, Ana L M, Marques, Maria Paula M, Gil, Ana M
Format: Article
Language:English
Subjects:
Amino acids
Biomarkers
Breast
Cancer therapies
Cell division
Cisplatin
Drug dosages
Fatty acids
Kidneys
Liver
Magnetic resonance spectroscopy
Metabolism
Metabolites
Metabolomics
NMR
Nuclear magnetic resonance
Ovaries
Polyamines
Urine
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Summary: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.
ISSN:2218-1989
2218-1989
DOI:10.3390/metabo9110279