https://m2.mtmt.hu/ eng 2026-06-24 10:23 JournalArticle 31203017 VALIDATED true * Megosztott szerzőség 0 false 2026-06-16T09:59:19.638+0000 2026-04-16T07:24:31.896+0000 2020-03-02T18:45:14.597+0000 true 10010125 Ferdinandy Péter /api/author/10010125 Author true 10010125 2026-06-16T07:47:25.198+0000 2023-09-02T15:34:18.177+0000 true 10039043 Milánkovics Róbert /api/admin/10039043 Admin true 10039043 Admin 10073918 /api/admin/10073918 Kovács Marcell true true 2024-09-09T07:21:55.189+0000 true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Brenner, Gábor B Hidden Cardiotoxicity of Rofecoxib Can be Revealed in Experimental Models of Ischemia/Reperfusion true true /api/journal/10051562 REVIEWED true false 10051562 false 10051562 true 2073-4409 Journal FOREIGN 9 3 551 551 17 2020 Cardiac adverse effects are among the leading causes of the discontinuation of clinical trials and the withdrawal of drugs from the market. The novel concept of 'hidden cardiotoxicity' is defined as cardiotoxicity of a drug that manifests in the diseased (e.g. ischemic/reperfused), but not in the healthy heart or as a drug-induced deterioration of cardiac stress adaptation (e.g. ischemic conditioning). Here, we aimed to test if the cardiotoxicity of a selective COX-2 inhibitor rofecoxib that was revealed during its clinical use, i.e., increased occurrence of proarrhythmic and thrombotic events, could have been revealed in early phases of drug development by using preclinical models of ischemia/reperfusion (I/R) injury. Rats that were treated with rofecoxib or vehicle for four weeks were subjected to 30 min. coronary artery occlusion and 120 min. reperfusion with or without cardioprotection that is induced by ischemic preconditioning (IPC). Rofecoxib increased overall the arrhythmias including ventricular fibrillation (VF) during I/R. The proarrhythmic effect of rofecoxib during I/R was not observed in the IPC group. Rofecoxib prolonged the action potential duration (APD) in isolated papillary muscles, which was not seen in the simulated IPC group. Interestingly, while showing hidden cardiotoxicity manifested as a proarrhythmic effect during I/R, rofecoxib decreased the infarct size and increased the survival of adult rat cardiac myocytes that were subjected to simulated I/R injury. This is the first demonstration that rofecoxib increased acute mortality due to its proarrhythmic effect via increased APD during I/R. Rofecoxib did not interfere with the cardiprotective effect of IPC; moreover, IPC was able to protect against rofecoxib-induced hidden cardiotoxicity. These results show that cardiac safety testing with simple preclinical models of I/R injury uncovers hidden cardiotoxicity of rofecoxib and might reveal the hidden cardiotoxicity of other drugs. 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class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" mtid="10052112"><a href="/gui2/?type=authors&mode=browse&sel=10052112" target="_blank">Brenner Gábor B (<span class="authorship-author-name">Brenner Gábor</span> <span class="authorAux-mtmt"> Kardiovaszkuláris farmakológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Pharmacology and Pharmacotherapy</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10055074"><a href="/gui2/?type=authors&mode=browse&sel=10055074" target="_blank">Makkos András (<span class="authorship-author-name">Makkos András</span> <span class="authorAux-mtmt"> orvos</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Pharmacology and Pharmacotherapy</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10051812"><a href="/gui2/?type=authors&mode=browse&sel=10051812" target="_blank">Nagy Csilla Terézia (<span class="authorship-author-name">Nagy Csilla Terézia</span> <span class="authorAux-mtmt"> kardiovaszkuláris megbetegedések</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Pharmacology and Pharmacotherapy</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10061054"><a href="/gui2/?type=authors&mode=browse&sel=10061054" target="_blank">Onódi Zsófia (<span class="authorship-author-name">Onódi Zsófia</span> <span class="authorAux-mtmt"> Farmakológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Pharmacology and Pharmacotherapy</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10074459"><a href="/gui2/?type=authors&mode=browse&sel=10074459" target="_blank">Sayour Nabil V (<span class="authorship-author-name">Sayour Viktor Nabil</span> <span class="authorAux-mtmt"> farmakológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Pharmacology and Pharmacotherapy</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10074629"><a href="/gui2/?type=authors&mode=browse&sel=10074629" target="_blank">Gergely Tamás G (<span class="authorship-author-name">Gergely Tamás G</span> <span class="authorAux-mtmt"> kardiovaszkuláris farmakológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Pharmacology and Pharmacotherapy</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10064374"><a href="/gui2/?type=authors&mode=browse&sel=10064374" target="_blank">Kiss Bernadett (<span class="authorship-author-name">Kiss Bernadett</span> <span class="authorAux-mtmt"> Farmakológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Pharmacology and Pharmacotherapy</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10027602"><a href="/gui2/?type=authors&mode=browse&sel=10027602" target="_blank">Görbe Anikó (<span class="authorship-author-name">Görbe Anikó</span> <span class="authorAux-mtmt"> orvostudomany</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Pharmacology and Pharmacotherapy; <span title="University of Szeged">SZTE</span>/<span title="Faculty of Medicine">ÁOK</span>/Department of Pharmacology and Pharmacotherapy</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10037547"><a href="/gui2/?type=authors&mode=browse&sel=10037547" target="_blank">Sághy Éva (<span class="authorship-author-name">Sághy Éva</span> <span class="authorAux-mtmt"> Gyógyszertudományok, farmakológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Pharmacology and Pharmacotherapy</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10017488"><a href="/gui2/?type=authors&mode=browse&sel=10017488" target="_blank">Zádori Zoltán S (<span class="authorship-author-name">Zádori Zoltán Sándor</span> <span class="authorAux-mtmt"> Farmakológia, gasztrointesztinális farmakológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Pharmacology and Pharmacotherapy</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10057402"><a href="/gui2/?type=authors&mode=browse&sel=10057402" target="_blank">Lázár Bernadette (<span class="authorship-author-name">Lázár Bernadette</span> <span class="authorAux-mtmt"> Farmakológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Pharmacology and Pharmacotherapy</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10040912"><a href="/gui2/?type=authors&mode=browse&sel=10040912" target="_blank">Baranyai Tamás (<span class="authorship-author-name">Baranyai Tamás</span> <span class="authorAux-mtmt"> Kardiológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Pharmacology and Pharmacotherapy</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10047823"><a href="/gui2/?type=authors&mode=browse&sel=10047823" target="_blank">Varga Richárd S (<span class="authorship-author-name">Varga Richárd Sándor</span> <span class="authorAux-mtmt"> Kísérletes szív-elektrofiziológia</span>) </a> </span> <span class="author-affil"><span title="University of Szeged">SZTE</span>/<span title="Faculty of Medicine">ÁOK</span>/Department of Pharmacology and Pharmacotherapy</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10027733"><a href="/gui2/?type=authors&mode=browse&sel=10027733" target="_blank">Husti Zoltán (<span class="authorship-author-name">Husti Zoltán</span> <span class="authorAux-mtmt"> Kísérletes kardiológia</span>) </a> </span> <span class="author-affil"><span title="University of Szeged">SZTE</span>/<span title="Faculty of Medicine">ÁOK</span>/Department of Pharmacology and Pharmacotherapy</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10001232"><a href="/gui2/?type=authors&mode=browse&sel=10001232" target="_blank">Varró András (<span class="authorship-author-name">Varró András</span> <span class="authorAux-mtmt"> Szívelektrofiziológia</span>) </a> </span> <span class="author-affil"><span title="University of Szeged">SZTE</span>/<span title="Faculty of Medicine">ÁOK</span>/Department of Pharmacology and Pharmacotherapy</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10015597"><a href="/gui2/?type=authors&mode=browse&sel=10015597" target="_blank">Tóthfalusi László (<span class="authorship-author-name">Tóthfalusi László</span> <span class="authorAux-mtmt"> Farmakometria</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Pharmacy">FP</span>/Department of Pharmacodynamics</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Schulz Rainer </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10001718"><a href="/gui2/?type=authors&mode=browse&sel=10001718" target="_blank">Baczkó István<sup>**</sup> (<span class="authorship-author-name">Baczkó István</span> <span class="authorAux-mtmt"> Kardiovaszkuláris farmakológia</span>) </a> </span> <span class="author-affil"><span title="University of Szeged">SZTE</span>/<span title="Faculty of Medicine">ÁOK</span>/Department of Pharmacology and Pharmacotherapy</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10026898"><a href="/gui2/?type=authors&mode=browse&sel=10026898" target="_blank">Giricz Zoltán<sup>**</sup> ✉ (<span class="authorship-author-name">Giricz Zoltán</span> <span class="authorAux-mtmt"> Biokémia, Farmakológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Pharmacology and Pharmacotherapy</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10010125"><a href="/gui2/?type=authors&mode=browse&sel=10010125" target="_blank">Ferdinandy Péter ✉ (<span class="authorship-author-name">Ferdinandy Péter</span> <span class="authorAux-mtmt"> Farmakológia, molekuláris medicina</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Pharmacology and Pharmacotherapy</span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;31203017" target="_blank">Hidden Cardiotoxicity of Rofecoxib Can be Revealed in Experimental Models of Ischemia/Reperfusion</a></div> <div> <span class="journal-title">CELLS</span> <span class="journal-issn">( <a target="_blank" href="https://portal.issn.org/resource/ISSN/2073-4409">2073-4409</a>)</span>: <span class="journal-volume">9</span> <span class="journal-issue">3</span> <span class="page"> Paper 551. 17 p. </span> <span class="year">(2020)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Language: English | </span> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.3390/cells9030551" target="_blank" href="https://doi.org/10.3390/cells9030551"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000529337400028" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000529337400028"> WoS </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:blue" title="8448" target="_blank" href="https://repo.lib.semmelweis.hu/handle/123456789/8448"> SE Repozitórium </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:blue" title="115670" target="_blank" href="https://real.mtak.hu/115670"> REAL </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85086863280" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85086863280"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="32111102" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=32111102&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:blue" title="18357" target="_blank" href="http://publicatio.bibl.u-szeged.hu/18357"> SZTE Publicatio </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Journal subject: Scopus - Medicine (miscellaneous)&nbsp;&nbsp;&nbsp;Rank:&nbsp;Q1</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="" class="citingPub-count">Citing papers: 25</span> | Independent citation: 12 | Self citation: 13 | Unknown citation: 0 | Number of citations in WoS: 22 | Number of citations in Scopus:&nbsp;25 | WoS/Scopus assigned:&nbsp;25 | Number of citations with DOI:&nbsp;25 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;31203017&sort=publishedYear,desc&sort=title"> Number of cited publications: 5 </a> </div> <div class="mtid"><span class="long-pub-mtid">Publication: 31203017</span> | <span class="status-data status-VALIDATED"> Validated </span> Core Citing | <span class="type-subtype">Journal Article ( Article ) </span> | <span class="pub-category">Scientific</span> | <span class="publication-sourceOfData">PubMed XML</span> </div> <div class="funder"> Az orvos-, egészségtudományi- és gyógyszerészképzés tudományos műhelyeinek fejlesztése(EFOP-3.6.3-VEKOP-16-2017-00009) Funder: EFOP-VEKOP, National Heart Program(NVKP-16-1-2016-0017) Funder: NRDIO, A szívizom repolarizációs rezerv proaritmiás szerepének tisztázása krónikus betegség modellekben(K-128851) Funder: NKFIH, GINOP-2.3.2-15-2016-00040(GINOP-2.3.2-15-2016-00040) Funder: NRDIO, (ÚNKP-18-4), (UNKP-19-3-I-SE-60) </div> <div class="lastModified">Last Modified: 2026.04.16. 09:24 Rita Csernyik (MTMT központi admin) </div> <div class="lockedBy">Centrally managed 2024.09.09. 09:21 Marcell Kovács (MTMT Közp., admin) </div> <pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Comments</u>: * Megosztott szerzőség</pre> </div></div>