{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:49:52Z","timestamp":1760150992698,"version":"build-2065373602"},"reference-count":79,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,22]],"date-time":"2022-01-22T00:00:00Z","timestamp":1642809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/50011\/2020 and UIDP\/50011\/2020; LAQV\/REQUIMTE FCT UIDB\/50006\/2020; UIDB\/00070\/2020","POCI-01-0145-FEDER-0016786, and Centro-01-0145-FEDER-029956","Portuguese National NMR Network (PTNMR), Infrastructure Project N\u00ba 022161","PD\/BD\/135460\/2017 ; SFRH\/BD\/145920\/2019"],"award-info":[{"award-number":["UIDB\/50011\/2020 and UIDP\/50011\/2020; LAQV\/REQUIMTE FCT UIDB\/50006\/2020; UIDB\/00070\/2020","POCI-01-0145-FEDER-0016786, and Centro-01-0145-FEDER-029956","Portuguese National NMR Network (PTNMR), Infrastructure Project N\u00ba 022161","PD\/BD\/135460\/2017 ; SFRH\/BD\/145920\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The new palladium agent Pd2Spermine (Spm) has been reported to exhibit promising cytotoxic properties, while potentially circumventing the known disadvantages associated to cisplatin therapeutics, namely acquired resistance and high toxicity. This work presents a nuclear magnetic resonance (NMR) metabolomics study of brain extracts obtained from healthy mice, to assess the metabolic impacts of the new Pd2Spm complex in comparison to that of cisplatin. The proton NMR spectra of both polar and nonpolar brain extracts were analyzed by multivariate and univariate statistics, unveiling several metabolite variations during the time course of exposition to each drug (1\u201348 h). The distinct time-course dependence of such changes revealed useful information on the drug-induced dynamics of metabolic disturbances and recovery periods, namely regarding amino acids, nucleotides, fatty acids, and membrane precursors and phospholipids. Putative biochemical explanations were proposed, based on existing pharmacokinetics data and previously reported metabolic responses elicited by the same metal complexes in the liver of the same animals. Generally, results suggest a more effective response of brain metabolism towards the possible detrimental effects of Pd2Spm, with more rapid recovery back to metabolites\u2019 control levels and, thus, indicating that the palladium drug may exert a more beneficial role than cDDP in relation to brain toxicity.<\/jats:p>","DOI":"10.3390\/pharmaceutics14020259","type":"journal-article","created":{"date-parts":[[2022,1,23]],"date-time":"2022-01-23T20:34:40Z","timestamp":1642970080000},"page":"259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Metabolic Impact of Anticancer Drugs Pd2Spermine and Cisplatin on the Brain of Healthy Mice"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4841-7860","authenticated-orcid":false,"given":"Tatiana J.","family":"Carneiro","sequence":"first","affiliation":[{"name":"Department of Chemistry and CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9257-7020","authenticated-orcid":false,"given":"Martin","family":"Vojtek","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4150-755 Porto, Portugal"}]},{"given":"Salom\u00e9","family":"Gon\u00e7alves-Monteiro","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4150-755 Porto, Portugal"}]},{"given":"Jo\u00e3o R.","family":"Neves","sequence":"additional","affiliation":[{"name":"Department of Chemistry and CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1280-3321","authenticated-orcid":false,"given":"Ana L. M. Batista de","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Molecular Physical-Chemistry R&D Unit, Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8391-0055","authenticated-orcid":false,"given":"Maria Paula M.","family":"Marques","sequence":"additional","affiliation":[{"name":"Molecular Physical-Chemistry R&D Unit, Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal"},{"name":"Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, 3000-456 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4668-9360","authenticated-orcid":false,"given":"Carmen","family":"Diniz","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4150-755 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3766-4364","authenticated-orcid":false,"given":"Ana M.","family":"Gil","sequence":"additional","affiliation":[{"name":"Department of Chemistry and CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/205698a0","article-title":"Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode","volume":"205","author":"Rosenberg","year":"1965","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/222385a0","article-title":"Platinum compounds: A new class of potent antitumour agents","volume":"222","author":"Rosenberg","year":"1969","journal-title":"Nature"},{"key":"ref_3","first-page":"843019","article-title":"Neurotoxicity caused by the treatment with platinum analogues","volume":"2011","author":"Amptoulach","year":"2011","journal-title":"Chemother. 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