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The present study aimed to examine the cardioprotective effects of perindopril on chronic ANT cardiotoxicity in a rabbit model previously validated with the cardioprotective agent dexrazoxane (DEX) with focus on post-treatment follow-up (FU). Chronic cardiotoxicity was induced by daunorubicin (DAU; 3 mg\/kg\/week for 10 weeks). Perindopril (0.05 mg\/kg\/day) was administered before and throughout chronic DAU treatment. After the completion of treatment, significant benefits were observed in perindopril co-treated animals, particularly full prevention of DAU-induced mortality and prevention or significant reductions in cardiac dysfunction, plasma cardiac troponin T (cTnT) levels, morphological damage, and most of the myocardial molecular alterations. However, these benefits significantly waned during 3 weeks of drug-free FU, which was not salvageable by administering a higher perindopril dose. In the longer (10-week) FU period, further worsening of left ventricular function and morphological damage occurred together with heart failure (HF)-related mortality. Continued perindopril treatment in the FU period did not reverse this trend but prevented HF-related mortality and reduced the severity of the progression of cardiac damage. These findings contrasted with the robust long-lasting protection observed previously for DEX in the same model. Hence, in the present study, perindopril provided only temporary control of ANT cardiotoxicity development, which may be associated with the lack of effects on ANT-induced and topoisomerase II \u03b2 (TOP2B)-dependent DNA damage responses in the heart.<\/jats:p>","DOI":"10.1042\/cs20210836","type":"journal-article","created":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T11:16:47Z","timestamp":1638962207000},"page":"139-161","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Primary prevention of chronic anthracycline cardiotoxicity with ACE inhibitor is temporarily effective in rabbits, but benefits wane in post-treatment follow-up"],"prefix":"10.1042","volume":"136","author":[{"given":"Zuzana","family":"Pokorn\u00e1","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine in Hradec Kr\u00e1lov\u00e9, Charles University, Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Koll\u00e1rov\u00e1-Br\u00e1zdov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine in Hradec Kr\u00e1lov\u00e9, Charles University, Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Len\u010dov\u00e1-Popelov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine in Hradec Kr\u00e1lov\u00e9, Charles University, Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduard","family":"Jirkovsk\u00fd","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine in Hradec Kr\u00e1lov\u00e9, Charles University, Hradec Kr\u00e1lov\u00e9, Czech Republic"},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University, Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Kube\u0161","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University, Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvona","family":"Mazurov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine in Hradec Kr\u00e1lov\u00e9, Charles University, Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Adamcov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine in Hradec Kr\u00e1lov\u00e9, Charles University, Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Hole\u010dkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Diagnostics, Faculty of Medicine in Hradec Kr\u00e1lov\u00e9, Charles University and University Hospital Hradec Kr\u00e1lov\u00e9, Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladim\u00edr","family":"Pali\u010dka","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Diagnostics, Faculty of Medicine in Hradec Kr\u00e1lov\u00e9, Charles University and University Hospital Hradec Kr\u00e1lov\u00e9, Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1\u0161","family":"\u0160im\u016fnek","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University, Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0145-7697","authenticated-orcid":false,"given":"Martin","family":"\u0160t\u011brba","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine in Hradec Kr\u00e1lov\u00e9, Charles University, Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2022,1,7]]},"reference":[{"key":"2022010711315577100_B1","doi-asserted-by":"publisher","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. 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