{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T06:38:23Z","timestamp":1773038303680,"version":"3.50.1"},"reference-count":57,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2017,10,11]],"date-time":"2017-10-11T00:00:00Z","timestamp":1507680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FARB (2014) University of Salerno"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The use of Doxorubicin (DOXO), a potent antineoplastic agent, is limited by the development of cardiotoxicity. DOXO-induced cardiotoxicity is multifactorial, although alterations in calcium homeostasis, seem to be involved. Since even the Connexin43 (Cx43) plays a pivotal role in these two phenomena, in this study we have analyzed the effects of DOXO on Cx43 expression and localization. Damage caused by anthracyclines on cardiomyocytes is immediate after each injection, in the present study we used a short-term model of DOXO-induced cardiomyopathy. C57BL\/6j female mice were randomly divided in groups and injected with DOXO (2 or 10 mg\/kg i.p.) for 1\u20133 or 7 days once every other day. Cardiac function was assessed by Echocardiography. Sarco\/endoplasmic reticulum Ca2+-ATPase (SERCAII) and phospholamban (PLB) expression were assessed by Western blot analysis, intracellular [Ca2+] were detected spectrofluorometrically by means of Fura-2 pentakis (acetoxymethyl) ester (FURA-2AM), and Cx43 and pCx43 expression and localization was analyzed by Western blot and confirmed by immunofluorescence analysis. DOXO induces impairment in Ca2+ homeostasis, already evident after a single administration, and affects Cx43 expression and localization. Our data suggest that DOXO-induced alterations in Ca2+ homeostasis causes in the cells the induction of compensatory mechanisms until a certain threshold, above which cardiac injury is triggered.<\/jats:p>","DOI":"10.3390\/ijms18102121","type":"journal-article","created":{"date-parts":[[2017,10,11]],"date-time":"2017-10-11T12:17:47Z","timestamp":1507724267000},"page":"2121","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Cardiotoxic Effects of Short-Term Doxorubicin Administration: Involvement of Connexin 43 in Calcium Impairment"],"prefix":"10.3390","volume":"18","author":[{"given":"Michela","family":"Pecoraro","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Fisciano (SA) 84084, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2930-8773","authenticated-orcid":false,"given":"Antonio","family":"Rodr\u00edguez-Sinovas","sequence":"additional","affiliation":[{"name":"Cardiovascular Diseases Research Group, Department of Cardiology, Vall d\u2019Hebron University Hospital and Research Institute, Universitat Aut\u00f2noma de Barcelona (UAB), Barcelona 08035, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2333-1630","authenticated-orcid":false,"given":"Stefania","family":"Marzocco","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Fisciano (SA) 84084, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2379-1960","authenticated-orcid":false,"given":"Michele","family":"Ciccarelli","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Salerno, Baronissi (SA) 84084, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8997-835X","authenticated-orcid":false,"given":"Guido","family":"Iaccarino","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Salerno, Baronissi (SA) 84084, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6899-6340","authenticated-orcid":false,"given":"Aldo","family":"Pinto","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Fisciano (SA) 84084, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9843-8443","authenticated-orcid":false,"given":"Ada","family":"Popolo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Fisciano (SA) 84084, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1034\/j.1600-0773.2003.930301.x","article-title":"Doxorubicin-induced cardiac mitochondrionopathy","volume":"93","author":"Wallace","year":"2003","journal-title":"Pharmacol. 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