Tatiana J Carneiro1, Rita Araújo1, Martin Vojtek2, Salomé Gonçalves-Monteiro2, Carmen Diniz2, Ana L M Batista de Carvalho3, M Paula M Marques3,4, Ana M Gil1. 1. Department of Chemistry and CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal. 2. LAQV/REQUIMTE, Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal. 3. R&D Unit "Molecular-Physical Chemistry", University of Coimbra, 3004-535 Coimbra, Portugal. 4. Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, 3000-456 Coimbra, Portugal.
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 (Pd2Spm) 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 Pd2Spm 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 Pd2Spm, 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 Pd2Spm administration.
pan class="Chemical">Pd(II)-compounds are presently regarded as promising antipan class="Disease">cancer drugs, as an alternative to pan class="Chemical">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 (Pd2Spm) 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 Pd2Spm 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 Pd2Spm, 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 Pd2Spm administration.
Authors: Martin Vojtek; Salomé Gonçalves-Monteiro; Patrícia Šeminská; Katarína Valová; Loreto Bellón; Patrícia Dias-Pereira; Franklim Marques; Maria P M Marques; Ana L M Batista de Carvalho; Helder Mota-Filipe; Isabel M P L V O Ferreira; Carmen Diniz Journal: Biomedicines Date: 2022-01-19
Authors: Tatiana J Carneiro; Martin Vojtek; Salomé Gonçalves-Monteiro; João R Neves; Ana L M Batista de Carvalho; Maria Paula M Marques; Carmen Diniz; Ana M Gil Journal: Pharmaceutics Date: 2022-01-22 Impact factor: 6.321