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We intended to study the cardiac pathways one week (short-term, control 1 [CTRL1] and DOX1 groups) or five months (long-term, CTRL2 and DOX2 groups) after DOX administration in adult male CD-1 mice. Control groups were given saline, and DOX groups received a 9.0 mg\/Kg cumulative dose. In the short-term, DOX decreased the content of AMP-activated protein kinase (AMPK) while the electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) increased compared to CTRL1, suggesting the upregulation of fatty acids oxidation. Moreover, mitofusin1 (Mfn1) content was decreased in DOX1, highlighting decreased mitochondrial fusion. In addition, increased B-cell lymphoma-2 associated X-protein (BAX) content in DOX1 pointed to the upregulation of apoptosis. Conversely, in the long-term, DOX decreased the citrate synthase (CS) activity and the content of Beclin1 and autophagy protein 5 (ATG5) compared to CTRL2, suggesting decreased mitochondrial density and autophagy. Our study demonstrates that molecular mechanisms elicited by DOX are modulated at different extents over time, supporting the differences on clinic cardiotoxic manifestations with time. Moreover, even five months after DOX administration, meaningful heart molecular changes occurred, reinforcing the need for the continuous cardiac monitoring of patients and determination of earlier biomarkers before clinical cardiotoxicity is set.<\/jats:p>","DOI":"10.3390\/ph16111613","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T10:51:37Z","timestamp":1700045497000},"page":"1613","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Metabolic Fingerprint of Doxorubicin-Induced Cardiotoxicity in Male CD-1 Mice Fades Away with Time While Autophagy Increases"],"prefix":"10.3390","volume":"16","author":[{"given":"Sofia Reis","family":"Brand\u00e3o","sequence":"first","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2775-3147","authenticated-orcid":false,"given":"Ana","family":"Reis-Mendes","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Maria Jo\u00e3o","family":"Neuparth","sequence":"additional","affiliation":[{"name":"Laboratory for Integrative and Translational Research in Population Health (ITR), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sports, University of Porto, 4200-450 Porto, Portugal"},{"name":"TOXRUN\u2014Toxicology Research Unit, University Institute of Health Sciences, CESPU, 4585-116 Gandra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3858-3494","authenticated-orcid":false,"given":"F\u00e9lix","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6872-4051","authenticated-orcid":false,"given":"Rita","family":"Ferreira","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0471-2756","authenticated-orcid":false,"given":"Vera Marisa","family":"Costa","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer Statistics, 2019","volume":"69","author":"Siegel","year":"2019","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1517\/14740338.4.2.219","article-title":"Toxicity of the Topoisomerase II Inhibitors","volume":"4","author":"Seiter","year":"2005","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1159\/000136248","article-title":"A Comparison of the Cardiovascular Actions of Daunomycin, Adriamycin and N-Acetyldaunomycin in Hamsters and Monkeys","volume":"6","author":"Herman","year":"1971","journal-title":"Pharmacology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1136\/bmj.3.5669.503","article-title":"Clinical Evaluation of Adriamycin, a New Antitumour Antibiotic","volume":"3","author":"Bonadonna","year":"1969","journal-title":"BMJ"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"105","DOI":"10.2217\/fca.12.73","article-title":"Using Cardiac Biomarkers and Treating Cardiotoxicity in Cancer","volume":"9","author":"Colombo","year":"2013","journal-title":"Future Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1080\/21548331.2018.1530831","article-title":"Cardiotoxicity of Cancer Chemotherapy in Clinical Practice","volume":"47","author":"Jain","year":"2019","journal-title":"Hosp. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1001\/jama.1991.03470120074036","article-title":"Cardiac Toxicity 4 to 20 Years after Completing Anthracycline Therapy","volume":"266","author":"Steinherz","year":"1991","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1200\/JCO.2004.06.022","article-title":"Enalapril to Prevent Cardiac Function Decline in Long-Term Survivors of Pediatric Cancer Exposed to Anthracyclines","volume":"22","author":"Silber","year":"2004","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"155250","DOI":"10.1016\/j.metabol.2022.155250","article-title":"Insights on the Molecular Targets of Cardiotoxicity Induced by Anticancer Drugs: A Systematic Review Based on Proteomic Findings","volume":"134","author":"Carvalho","year":"2022","journal-title":"Metabolism"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1038\/nm.2919","article-title":"Identification of the Molecular Basis of Doxorubicin-Induced Cardiotoxicity","volume":"18","author":"Zhang","year":"2012","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1172\/JCI72931","article-title":"Cardiotoxicity of Doxorubicin Is Mediated through Mitochondrial Iron Accumulation","volume":"124","author":"Ichikawa","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"75","DOI":"10.2174\/1389200216666151103114926","article-title":"The Role of the Metabolism of Anticancer Drugs in Their Induced-Cardiotoxicity","volume":"17","author":"Sousa","year":"2015","journal-title":"Curr. Drug Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.mito.2016.07.005","article-title":"Cardiac Cytochrome c and Cardiolipin Depletion during Anthracycline-Induced Chronic Depression of Mitochondrial Function","volume":"30","author":"Pereira","year":"2016","journal-title":"Mitochondrion"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.ejphar.2017.10.043","article-title":"Molecular Mechanism of Doxorubicin-Induced Cardiomyopathy\u2014An Update","volume":"818","author":"Renu","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"119760","DOI":"10.1016\/j.lfs.2021.119760","article-title":"An Update of the Molecular Mechanisms Underlying Doxorubicin plus Trastuzumab Induced Cardiotoxicity","volume":"280","author":"Anjos","year":"2021","journal-title":"Life Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"152852","DOI":"10.1016\/j.tox.2021.152852","article-title":"Exploring the Aging Effect of the Anticancer Drugs Doxorubicin and Mitoxantrone on Cardiac Mitochondrial Proteome Using a Murine Model","volume":"459","author":"Domingues","year":"2021","journal-title":"Toxicology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.yjmcc.2022.08.136","article-title":"Doxorubicin-Induced Cardiotoxicity Is Associated with a Change in High Density Lipoprotein Subclasses in a Mouse Breast Cancer Model","volume":"173","author":"Abrahams","year":"2022","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.jaccao.2022.01.102","article-title":"Does Cardiovascular Mortality Overtake Cancer Mortality During Cancer Survivorship?","volume":"4","author":"Strongman","year":"2022","journal-title":"JACC CardioOncol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Reis-Mendes, A., Ferreira, M., Padr\u00e3o, A.I., Duarte, J.A., Duarte-Ara\u00fajo, M., Remi\u00e3o, F., Carvalho, F., Sousa, E., Bastos, M.L., and Costa, V.M. (2023). The Role of Nrf2 and Inflammation on the Dissimilar Cardiotoxicity of Doxorubicin in Two-Time Points: A Cardio-Oncology In Vivo Study Through Time. Inflammation, in press.","DOI":"10.1007\/s10753-023-01908-0"},{"key":"ref_20","unstructured":"Terjung, R. (2015). Comprehensive Physiology, Wiley."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Krause, N., and Wegner, A. (2020). Fructose Metabolism in Cancer. Cells, 9.","DOI":"10.3390\/cells9122635"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s10545-010-9104-8","article-title":"The Enzymology of Mitochondrial Fatty Acid Beta-Oxidation and Its Application to Follow-up Analysis of Positive Neonatal Screening Results","volume":"33","author":"Wanders","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-94-007-2869-1_1","article-title":"The Oxidative Phosphorylation System in Mammalian Mitochondria","volume":"Volume 942","author":"Scatena","year":"2012","journal-title":"Advances in Mitochondrial Medicine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3349","DOI":"10.1113\/jphysiol.2012.230185","article-title":"Biomarkers of Mitochondrial Content in Skeletal Muscle of Healthy Young Human Subjects: Biomarkers of Mitochondrial Content","volume":"590","author":"Larsen","year":"2012","journal-title":"J. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s10557-016-6710-1","article-title":"Mitochondrial-Shaping Proteins in Cardiac Health and Disease\u2014The Long and the Short of It!","volume":"31","author":"Ong","year":"2017","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s10741-016-9561-8","article-title":"Mitochondrial Pathways to Cardiac Recovery: TFAM","volume":"21","author":"Kunkel","year":"2016","journal-title":"Heart Fail. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.7150\/thno.71102","article-title":"Cardiomyocytic FoxP3 Is Involved in Parkin-Mediated Mitophagy during Cardiac Remodeling and the Regulatory Role of Triptolide","volume":"12","author":"Pan","year":"2022","journal-title":"Theranostics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1007\/s12265-010-9174-x","article-title":"Mitochondrial Pruning by Nix and BNip3: An Essential Function for Cardiac-Expressed Death Factors","volume":"3","author":"Dorn","year":"2010","journal-title":"J Cardiovasc. Transl. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: A Review of Programmed Cell Death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Vajravelu, B.N., Hong, K.U., Al-Maqtari, T., Cao, P., Keith, M.C.L., Wysoczynski, M., Zhao, J., Moore IV, J.B., and Bolli, R. (2015). C-Kit Promotes Growth and Migration of Human Cardiac Progenitor Cells via the PI3K-AKT and MEK-ERK Pathways. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140798"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.tcb.2007.07.004","article-title":"The C\/EBP Family of Transcription Factors: A Paradigm for Interaction between Gene Expression and Proliferation Control","volume":"17","author":"Nerlov","year":"2007","journal-title":"Trends Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/s41392-022-01153-1","article-title":"Exercise Training Maintains Cardiovascular Health: Signaling Pathways Involved and Potential Therapeutics","volume":"7","author":"Chen","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"117242","DOI":"10.1016\/j.lfs.2019.117242","article-title":"Correlation between Mouse Age and Human Age in Anti-Tumor Research: Significance and Method Establishment","volume":"242","author":"Wang","year":"2020","journal-title":"Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1002\/open.201900113","article-title":"Fatty Acid Binding to Human Serum Albumin in Blood Serum Characterized by EPR Spectroscopy","volume":"8","author":"Haeri","year":"2019","journal-title":"ChemistryOpen"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Reis-Mendes, A., Padr\u00e3o, A.I., Duarte, J.A., Gon\u00e7alves-Monteiro, S., Duarte-Ara\u00fajo, M., Remi\u00e3o, F., Carvalho, F., Sousa, E., Bastos, M.L., and Costa, V.M. (2021). Role of Inflammation and Redox Status on Doxorubicin-Induced Cardiotoxicity in Infant and Adult CD-1 Male Mice. Biomolecules, 11.","DOI":"10.3390\/biom11111725"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.tox.2010.01.019","article-title":"Metabolic Remodeling Associated with Subchronic Doxorubicin Cardiomyopathy","volume":"270","author":"Carvalho","year":"2010","journal-title":"Toxicology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4705","DOI":"10.1016\/j.jprot.2012.02.004","article-title":"Cardiac Phosphoproteome Reveals Cell Signaling Events Involved in Doxorubicin Cardiotoxicity","volume":"75","author":"Gratia","year":"2012","journal-title":"J. Proteom."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.jprot.2011.02.013","article-title":"Analysis of Proteome Changes in Doxorubicin-Treated Adult Rat Cardiomyocyte","volume":"74","author":"Kumar","year":"2011","journal-title":"J. Proteom."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1161\/01.RES.0000258446.23525.37","article-title":"AMP-Activated Protein Kinase in the Heart: Role During Health and Disease","volume":"100","author":"Arad","year":"2007","journal-title":"Circ. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1038\/s41569-021-00569-6","article-title":"PPAR Control of Metabolism and Cardiovascular Functions","volume":"18","author":"Montaigne","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Yoon, C., Kim, H., Mishchenko, N., Vasileva, E., Fedoreyev, S., Stonik, V., and Han, J. (2018). Spinochrome D Attenuates Doxorubicin-Induced Cardiomyocyte Death via Improving Glutathione Metabolism and Attenuating Oxidative Stress. Mar. Drugs, 17.","DOI":"10.3390\/md17010002"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ding, Q., Qi, Y., and Tsang, S.-Y. (2021). Mitochondrial Biogenesis, Mitochondrial Dynamics, and Mitophagy in the Maturation of Cardiomyocytes. Cells, 10.","DOI":"10.3390\/cells10092463"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e005234","DOI":"10.1161\/CIRCHEARTFAILURE.118.005234","article-title":"Doxorubicin Exposure Causes Subacute Cardiac Atrophy Dependent on the Striated Muscle\u2013Specific Ubiquitin Ligase MuRF1","volume":"12","author":"Willis","year":"2019","journal-title":"Circ. Heart Fail."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3390\/oxygen1010002","article-title":"Oxygen Is Instrumental for Biological Signaling: An Overview","volume":"1","author":"Hancock","year":"2021","journal-title":"Oxygen"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7901735","DOI":"10.1155\/2019\/7901735","article-title":"Protection against Doxorubicin-Induced Cytotoxicity by Geniposide Involves AMPK \u03b1 Signaling Pathway","volume":"2019","author":"Meng","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"jeb.208074","DOI":"10.1242\/jeb.208074","article-title":"Cardiac Mitochondrial Function, Nitric Oxide Sensitivity and Lipid Composition Following Hypoxia Acclimation in Sablefish","volume":"222","author":"Gerber","year":"2019","journal-title":"J. Exp. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Tang, S.-W., Ducroux, A., Jeang, K.-T., and Neuveut, C. (2012). Impact of Cellular Autophagy on Viruses: Insights from Hepatitis B Virus and Human Retroviruses. J. Biomed. Sci., 19.","DOI":"10.1186\/1423-0127-19-92"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Li, M., Russo, M., Pirozzi, F., Tocchetti, C.G., and Ghigo, A. (2020). Autophagy and Cancer Therapy Cardiotoxicity: From Molecular Mechanisms to Therapeutic Opportunities. Biochim. Biophys. Acta BBA Mol. Cell Res., 1867.","DOI":"10.1016\/j.bbamcr.2019.06.007"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1039\/c8pp00536b","article-title":"Heat Shock Protein 27 Modulates Autophagy and Promotes Cell Survival after Photodynamic Therapy","volume":"18","author":"Sanabria","year":"2019","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1096\/fj.07-9574LSF","article-title":"Dose Translation from Animal to Human Studies Revisited","volume":"22","author":"Nihal","year":"2008","journal-title":"FASEB J."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Brand\u00e3o, S.R., Reis-Mendes, A., Ara\u00fajo, M.D., Neuparth, M.J., Rocha, H., Carvalho, F., Ferreira, R., and Costa, V.M. (2023). Cardiac Molecular Remodeling by Anticancer Drugs: Doxorubicin Affects More Metabolism While Mitoxantrone Impacts More Autophagy in Adult CD-1 Male Mice. Biomolecules, 13.","DOI":"10.3390\/biom13060921"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1042\/bj1250115","article-title":"Regulation of Adipose Tissue Pyruvate Dehydrogenase by Insulin and Other Hormones","volume":"125","author":"Coore","year":"1971","journal-title":"Biochem. 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