{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T23:51:37Z","timestamp":1781221897188,"version":"3.54.1"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T00:00:00Z","timestamp":1686787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010621","name":"Medical University of Lublin","doi-asserted-by":"publisher","award":["DS38"],"award-info":[{"award-number":["DS38"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010621","name":"Medical University of Lublin","doi-asserted-by":"publisher","award":["DS380"],"award-info":[{"award-number":["DS380"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The anticancer efficacy of doxorubicin (DOX) is dose-limited because of cardiomyopathy, the most significant adverse effect. Initially, cardiotoxicity develops clinically silently, but it eventually appears as dilated cardiomyopathy with a very poor prognosis. Dexrazoxane (DEX) is the only FDA-approved drug to prevent the development of anthracycline cardiomyopathy, but its efficacy is insufficient. Carvedilol (CVD) is another product being tested in clinical trials for the same indication. This study\u2019s objective was to evaluate anthracycline cardiotoxicity in rats treated with CVD in combination with DEX. The studies were conducted using male Wistar rats receiving DOX (1.6 mg\/kg b.w. i.p., cumulative dose: 16 mg\/kg b.w.), DOX and DEX (25 mg\/kg b.w. i.p.), DOX and CVD (1 mg\/kg b.w. i.p.), or a combination (DOX + DEX + CVD) for 10 weeks. Afterward, in the 11th and 21st weeks of the study, echocardiography (ECHO) was performed, and the tissues were collected. The addition of CVD to DEX as a cardioprotective factor against DOX had no favorable advantages in terms of functional (ECHO), morphological (microscopic evaluation), and biochemical alterations (cardiac troponin I and brain natriuretic peptide levels), as well as systemic toxicity (mortality and presence of ascites). Moreover, alterations caused by DOX were abolished at the tissue level by DEX; however, when CVD was added, the persistence of DOX-induced unfavorable alterations was observed. The addition of CVD normalized the aberrant expression of the vast majority of indicated genes in the DOX + DEX group. Overall, the results indicate that there is no justification to use a simultaneous treatment of DEX and CVD in DOX-induced cardiotoxicity.<\/jats:p>","DOI":"10.3390\/ijms241210202","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T01:31:31Z","timestamp":1686879091000},"page":"10202","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Lack of Synergy between Carvedilol and the Preventive Effect of Dexrazoxane in the Model of Chronic Anthracycline-Induced Cardiomyopathy"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9915-0719","authenticated-orcid":false,"given":"Jaroslaw","family":"Szponar","sequence":"first","affiliation":[{"name":"Toxicology Clinic, Faculty of Medicine, Medical University of Lublin, 100 Krasnik Avenue, 20-550 Lublin, Poland"},{"name":"Clinical Department of Toxicology and Cardiology, Regional Specialist Hospital, 100 Krasnik Avenue, 20-550 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin","family":"Ciechanski","sequence":"additional","affiliation":[{"name":"Clinical Department of Cardiology, Regional Specialist Hospital, 100 Krasnik Avenue, 20-550 Lublin, Poland"},{"name":"Chair and Department of Toxicology, Medical University of Lublin, 8b Jaczewski Street, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3375-3821","authenticated-orcid":false,"given":"Marta","family":"Ostrowska-Lesko","sequence":"additional","affiliation":[{"name":"Chair and Department of Toxicology, Medical University of Lublin, 8b Jaczewski Street, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Gorska","sequence":"additional","affiliation":[{"name":"Toxicology Clinic, Faculty of Medicine, Medical University of Lublin, 100 Krasnik Avenue, 20-550 Lublin, Poland"},{"name":"Clinical Department of Toxicology and Cardiology, Regional Specialist Hospital, 100 Krasnik Avenue, 20-550 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Tchorz","sequence":"additional","affiliation":[{"name":"Toxicology Clinic, Faculty of Medicine, Medical University of Lublin, 100 Krasnik Avenue, 20-550 Lublin, Poland"},{"name":"Clinical Department of Toxicology and Cardiology, Regional Specialist Hospital, 100 Krasnik Avenue, 20-550 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Dabrowska","sequence":"additional","affiliation":[{"name":"Chair and Department of Toxicology, Medical University of Lublin, 8b Jaczewski Street, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaroslaw","family":"Dudka","sequence":"additional","affiliation":[{"name":"Chair and Department of Toxicology, Medical University of Lublin, 8b Jaczewski Street, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2903-4912","authenticated-orcid":false,"given":"Marek","family":"Murias","sequence":"additional","affiliation":[{"name":"Chair and Department of Toxicology, Poznan University of Medical Sciences, 30 Dojazd Street, 60-572 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1991-190X","authenticated-orcid":false,"given":"Micha\u0142","family":"Kowalczyk","sequence":"additional","affiliation":[{"name":"First Department of Anaesthesiology and Intensive Care, Medical University of Lublin, ul. Jaczewskiego 8, 20-954 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2027-9681","authenticated-orcid":false,"given":"Agnieszka","family":"Korga-Plewko","sequence":"additional","affiliation":[{"name":"Independent Medical Biology Unit, Medical University of Lublin, 8b Jaczewski Street, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slawomir","family":"Mandziuk","sequence":"additional","affiliation":[{"name":"Department of Pneumology, Oncology and Allergology, Medical University of Lublin, 8 Jaczewski Street, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1124\/pr.56.2.6","article-title":"Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity","volume":"56","author":"Minotti","year":"2004","journal-title":"Pharmacol. Rev."},{"key":"ref_2","first-page":"CD003917","article-title":"Cardioprotective Interventions for Cancer Patients Receiving Anthracyclines","volume":"2011","author":"Caron","year":"2011","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Deng, S., Yan, T., Jendrny, C., Nemecek, A., Vincetic, M., G\u00f6dtel-Armbrust, U., and Wojnowski, L. (2014). Dexrazoxane May Prevent Doxorubicin-Induced DNA Damage via Depleting Both Topoisomerase II Isoforms. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-842"},{"key":"ref_4","first-page":"e008209","article-title":"Clinically Translatable Prevention of Anthracycline Cardiotoxicity by Dexrazoxane Is Mediated by Topoisomerase II Beta and Not Metal Chelation","volume":"14","author":"Karabanovich","year":"2021","journal-title":"Circ. Heart Fail."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/sj.bjp.0707294","article-title":"Dexrazoxane Prevents Doxorubicin-Induced Long-Term Cardiotoxicity and Protects Myocardial Mitochondria from Genetic and Functional Lesions in Rats","volume":"151","author":"Lebrecht","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"113903","DOI":"10.1016\/j.biopha.2022.113903","article-title":"Research Progress of Therapeutic Drugs for Doxorubicin-Induced Cardiomyopathy","volume":"156","author":"Chen","year":"2022","journal-title":"Biomed. Pharmacother. Biomed. Pharmacother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.annonc.2019.10.023","article-title":"Management of Cardiac Disease in Cancer Patients throughout Oncological Treatment: ESMO Consensus Recommendations","volume":"31","author":"Curigliano","year":"2020","journal-title":"Ann. Oncol. Off. J. Eur. Soc. Med. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1001\/jamaoncol.2021.3395","article-title":"Cardioprotective Strategy for Patients With Nonmetastatic Breast Cancer Who Are Receiving an Anthracycline-Based Chemotherapy: A Randomized Clinical Trial","volume":"7","author":"Livi","year":"2021","journal-title":"JAMA Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1093\/eurheartj\/ehw128","article-title":"2016 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC)Developed with the Special Contribution of the Heart Failure Association (HFA) of the ESC","volume":"37","author":"Ponikowski","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1089\/ars.2012.4795","article-title":"Oxidative Stress, Redox Signaling, and Metal Chelation in Anthracycline Cardiotoxicity and Pharmacological Cardioprotection","volume":"18","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"H1453","DOI":"10.1152\/ajpheart.00554.2015","article-title":"Drug-Induced Mitochondrial Dysfunction and Cardiotoxicity","volume":"309","author":"Varga","year":"2015","journal-title":"Am. J. Physiol.\u2013Heart Circ. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1002\/med.21280","article-title":"Doxorubicin-Induced Cardiotoxicity: From Bioenergetic Failure and Cell Death to Cardiomyopathy","volume":"34","author":"Carvalho","year":"2014","journal-title":"Med. Res. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1124\/mol.119.115725","article-title":"Insights into Doxorubicin-Induced Cardiotoxicity: Molecular Mechanisms, Preventive Strategies, and Early Monitoring","volume":"96","author":"Wenningmann","year":"2019","journal-title":"Mol. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1080\/08880010701451244","article-title":"Toxicity Prevention with Amifostine in Pediatric Osteosarcoma Patients Treated with Cisplatin and Doxorubicin","volume":"24","year":"2007","journal-title":"Pediatr. Hematol. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/S1734-1140(09)70018-0","article-title":"Anthracycline-Induced Cardiotoxicity: Overview of Studies Examining the Roles of Oxidative Stress and Free Cellular Iron","volume":"61","author":"Hrdina","year":"2009","journal-title":"Pharmacol. Rep. PR"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.crvi.2005.08.007","article-title":"Alterations in Myocardial Energy Metabolism Induced by the Anti-Cancer Drug Doxorubicin","volume":"329","author":"Wallimann","year":"2006","journal-title":"C. R. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.yjmcc.2006.06.009","article-title":"New Insights into Doxorubicin-Induced Cardiotoxicity: The Critical Role of Cellular Energetics","volume":"41","author":"Zaugg","year":"2006","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Rocca, C., De Francesco, E.M., Pasqua, T., Granieri, M.C., De Bartolo, A., Gallo Cantafio, M.E., Muoio, M.G., Gentile, M., Neri, A., and Angelone, T. (2022). Mitochondrial Determinants of Anti-Cancer Drug-Induced Cardiotoxicity. Biomedicines, 10.","DOI":"10.3390\/biomedicines10030520"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0005-2728(99)00011-0","article-title":"Cardioselective and Cumulative Oxidation of Mitochondrial DNA Following Subchronic Doxorubicin Administration","volume":"1411","author":"Serrano","year":"1999","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1016\/j.freeradbiomed.2003.08.005","article-title":"The Oral Iron Chelator ICL670A (Deferasirox) Does Not Protect Myocytes against Doxorubicin","volume":"35","author":"Hasinoff","year":"2003","journal-title":"Free Radic. Biol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101394","DOI":"10.1016\/j.redox.2019.101394","article-title":"Teaching the Basics of the Mechanism of Doxorubicin-Induced Cardiotoxicity: Have We Been Barking up the Wrong Tree?","volume":"29","author":"Kalyanaraman","year":"2020","journal-title":"Redox Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/j.jacc.2014.06.1167","article-title":"Prevention of Anthracycline-Induced Cardiotoxicity: Challenges and Opportunities","volume":"64","author":"Vejpongsa","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_23","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_24","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1097\/FJC.0000000000000470","article-title":"Cardioprotective Effects of Carvedilol in Inhibiting Doxorubicin-Induced Cardiotoxicity","volume":"69","author":"Nabati","year":"2017","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1159\/000442722","article-title":"Carvedilol Administration Can Prevent Doxorubicin-Induced Cardiotoxicity: A Double-Blind Randomized Trial","volume":"134","author":"Hosseini","year":"2016","journal-title":"Cardiology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1016\/j.jacc.2018.02.049","article-title":"Carvedilol for Prevention of Chemotherapy-Related Cardiotoxicity","volume":"71","author":"Avila","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"147","DOI":"10.2174\/1570161053586903","article-title":"Are the Antioxidant Properties of Carvedilol Important for the Protection of Cardiac Mitochondria?","volume":"3","author":"Oliveira","year":"2005","journal-title":"Curr. Vasc. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1177\/2047487319870344","article-title":"Oxidative Stress and Inflammation in the Evolution of Heart Failure: From Pathophysiology to Therapeutic Strategies","volume":"27","author":"Aimo","year":"2020","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.freeradbiomed.2021.03.045","article-title":"Natural and Synthetic Antioxidants Targeting Cardiac Oxidative Stress and Redox Signaling in Cardiometabolic Diseases","volume":"169","author":"Lazou","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Wang, W., and Kang, P.M. (2020). Oxidative Stress and Antioxidant Treatments in Cardiovascular Diseases. Antioxidants, 9.","DOI":"10.3390\/antiox9121292"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Mandziuk, S., Gieroba, R., Korga, A., Matysiak, W., Jodlowska-Jedrych, B., Burdan, F., Poleszak, E., Kowalczyk, M., Grzycka-Kowalczyk, L., and Korobowicz, E. (2015). The Differential Effects of Green Tea on Dose-Dependent Doxorubicin Toxicity. Food Nutr. Res., 59.","DOI":"10.3402\/fnr.v59.29754"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/S0008-6363(98)00009-1","article-title":"A Small Animal Model of Non-Ischemic Cardiomyopathy and Its Evaluation by Transthoracic Echocardiography","volume":"39","author":"Schwarz","year":"1998","journal-title":"Cardiovasc. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"49","DOI":"10.4166\/kjg.2018.72.2.49","article-title":"Ascites","volume":"72","author":"Jeong","year":"2018","journal-title":"Korean J. Gastroenterol. Taehan Sohwagi Hakhoe Chi"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1152\/physrev.00015.2009","article-title":"Myocardial Fatty Acid Metabolism in Health and Disease","volume":"90","author":"Lopaschuk","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1152\/physrev.00006.2004","article-title":"Myocardial Substrate Metabolism in the Normal and Failing Heart","volume":"85","author":"Stanley","year":"2005","journal-title":"Physiol. Rev."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/12\/10202\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:56:03Z","timestamp":1760126163000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/12\/10202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,15]]},"references-count":35,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["ijms241210202"],"URL":"https:\/\/doi.org\/10.3390\/ijms241210202","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,15]]}}}