{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:41:27Z","timestamp":1760244087403,"version":"build-2065373602"},"reference-count":90,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CICECO-Aveiro Institute of Materials project","award":["UIDB\/50011\/2020","UIDP\/50011\/2020","LA\/P\/0006\/2020","UIDB\/50006\/2020","UIDB\/00070\/2020","POCI-01-0145-FEDER-0016786","022161","PD\/BD\/135460\/2017"],"award-info":[{"award-number":["UIDB\/50011\/2020","UIDP\/50011\/2020","LA\/P\/0006\/2020","UIDB\/50006\/2020","UIDB\/00070\/2020","POCI-01-0145-FEDER-0016786","022161","PD\/BD\/135460\/2017"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)","award":["UIDB\/50011\/2020","UIDP\/50011\/2020","LA\/P\/0006\/2020","UIDB\/50006\/2020","UIDB\/00070\/2020","POCI-01-0145-FEDER-0016786","022161","PD\/BD\/135460\/2017"],"award-info":[{"award-number":["UIDB\/50011\/2020","UIDP\/50011\/2020","LA\/P\/0006\/2020","UIDB\/50006\/2020","UIDB\/00070\/2020","POCI-01-0145-FEDER-0016786","022161","PD\/BD\/135460\/2017"]}]},{"name":"Infrastructure Project","award":["UIDB\/50011\/2020","UIDP\/50011\/2020","LA\/P\/0006\/2020","UIDB\/50006\/2020","UIDB\/00070\/2020","POCI-01-0145-FEDER-0016786","022161","PD\/BD\/135460\/2017"],"award-info":[{"award-number":["UIDB\/50011\/2020","UIDP\/50011\/2020","LA\/P\/0006\/2020","UIDB\/50006\/2020","UIDB\/00070\/2020","POCI-01-0145-FEDER-0016786","022161","PD\/BD\/135460\/2017"]}]},{"name":"Ph.D. Program in Medicines and Pharmaceutical Innovation (i3DU)","award":["UIDB\/50011\/2020","UIDP\/50011\/2020","LA\/P\/0006\/2020","UIDB\/50006\/2020","UIDB\/00070\/2020","POCI-01-0145-FEDER-0016786","022161","PD\/BD\/135460\/2017"],"award-info":[{"award-number":["UIDB\/50011\/2020","UIDP\/50011\/2020","LA\/P\/0006\/2020","UIDB\/50006\/2020","UIDB\/00070\/2020","POCI-01-0145-FEDER-0016786","022161","PD\/BD\/135460\/2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cisplatin (cDDP)-based chemotherapy is often limited by severe deleterious effects (nephrotoxicity, hepatotoxicity and neurotoxicity). The polynuclear palladium(II) compound Pd2Spermine (Pd2Spm) has emerged as a potential alternative drug, with favorable pharmacokinetic\/pharmacodynamic properties. This paper reports on a Nuclear Magnetic Resonance metabolomics study to (i) characterize the response of mice brain and liver to Pd2Spm, compared to cDDP, and (ii) correlate brain-liver metabolic variations. Multivariate and correlation analysis of the spectra of polar and lipophilic brain and liver extracts from an MDA-MB-231 cell-derived mouse model revealed a stronger impact of Pd2Spm on brain metabolome, compared to cDDP. This was expressed by changes in amino acids, inosine, cholate, pantothenate, fatty acids, phospholipids, among other compounds. Liver was less affected than brain, with cDDP inducing more metabolite changes. Results suggest that neither drug induces neuronal damage or inflammation, and that Pd2Spm seems to lead to enhanced brain anti-inflammatory and antioxidant mechanisms, regulation of brain bioactive metabolite pools and adaptability of cell membrane characteristics. The cDDP appears to induce higher extension of liver damage and an enhanced need for liver regeneration processes. This work demonstrates the usefulness of untargeted metabolomics in evaluating drug impact on multiple organs, while confirming Pd2Spm as a promising replacement of cDDP.<\/jats:p>","DOI":"10.3390\/ijms232213773","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T01:48:08Z","timestamp":1668044888000},"page":"13773","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of Pd2Spermine on Mice Brain-Liver Axis Metabolism Assessed by NMR Metabolomics"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4841-7860","authenticated-orcid":false,"given":"Tatiana J.","family":"Carneiro","sequence":"first","affiliation":[{"name":"Department of Chemistry, CICECO\u2014Aveiro 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\u2014Associated Laboratory for Green Chemistry of the Network of Chemistry and Technology, 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\u2014Associated Laboratory for Green Chemistry of the Network of Chemistry and Technology, Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4150-755 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1280-3321","authenticated-orcid":false,"given":"Ana L. M.","family":"Batista de 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\u2014Associated Laboratory for Green Chemistry of the Network of Chemistry and Technology, 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, CICECO\u2014Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,9]]},"reference":[{"key":"ref_1","first-page":"287353","article-title":"Platinum and palladium polyamine complexes as anticancer agents: The structural factor","volume":"2013","author":"Marques","year":"2013","journal-title":"Hindawi"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.drudis.2019.02.012","article-title":"Anticancer activity of palladium-based complexes against triple negative breast cancer","volume":"24","author":"Vojtek","year":"2019","journal-title":"Drug Discov. 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