Novel Insights into Mice Multi-Organ Metabolism upon Exposure to a Potential Anticancer Pd(II)-Agent
authors Carneiro, TJ; Araujo, R; Vojtek, M; Goncalves-Monteiro, S; Diniz, C; de Carvalho, ALMB; Marques, MPM; Gil, AM
nationality International
author keywords palladium(II)-drugs; Pd(2)Spm; cisplatin; mice; NMR metabolomics; tissue extracts
abstract Pd(II)-compounds are presently regarded as promising anticancer drugs, as an alternative to Pt(II)-based drugs (e.g., cisplatin), which typically trigger severe side-effects and acquired resistance. Dinuclear Pd(II) complexes with biogenic polyamines such as spermine (Pd(2)Spm) have exhibited particularly beneficial cytotoxic properties, hence unveiling the importance of understanding their impact on organism metabolism. The present study reports the first nuclear magnetic resonance (NMR)-based metabolomics study to assess the in vivo impact of Pd(2)Spm on the metabolism of healthy mice, to identify metabolic markers with possible relation to biotoxicity/side-effects and their dynamics. The changes in the metabolic profiles of both aqueous and lipophilic extracts of mice kidney, liver, and breast tissues were evaluated, as a function of drug-exposure time, using cisplatin as a reference drug. A putative interpretation was advanced for the metabolic deviations specifically triggered by Pd(2)Spm, this compound generally inducing faster metabolic response and recovery to control levels for all organs tested, compared to cisplatin (except for kidney lipid metabolism). These results constitute encouraging preliminary metabolic data suggestive of potential lower negative effects of Pd(2)Spm administration.
publisher MDPI
isbn 2218-1989
year published 2021
volume 11
issue 2
digital object identifier (doi) 10.3390/metabo11020114
web of science category 16
subject category Biochemistry & Molecular Biology
unique article identifier WOS:000622793100001
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