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Given this, rat hearts were perfused with Casiopeinas or Doxorubicin and the effects on mechanical performance, energetics, and mitochondrial function were measured. As well, the effects of Casiopeinas\u2010triggered cell death were explored in isolated cardiomyocytes. Casiopeinas III\u2010Ea, II\u2010gly, and III\u2010ia induced a progressive and sustained inhibition of heart contractile function that was dose\u2010 and time\u2010dependent with an IC<jats:sub>50<\/jats:sub> of 1.3\u2009\u00b1\u20090.2, 5.5\u2009\u00b1\u20090.5, and 10\u2009\u00b1\u20090.7\u2009<jats:italic>\u03bc<\/jats:italic>M, correspondingly. Myocardial oxygen consumption was not modified at their respective IC<jats:sub>50<\/jats:sub>, although ATP levels were significantly reduced, indicating energy impairment. Isolated mitochondria from Casiopeinas\u2010treated hearts showed a significant loss of membrane potential and reduction of mitochondrial Ca<jats:sup>2+<\/jats:sup> retention capacity. Interestingly, Cyclosporine A inhibited Casiopeinas\u2010induced mitochondrial Ca<jats:sup>2+<\/jats:sup> release, which suggests the involvement of the mitochondrial permeability transition pore opening. In addition, Casiopeinas reduced the viability of cardiomyocytes and stimulated the activation of caspases 3, 7, and 9, demonstrating a cell death mitochondrial\u2010dependent mechanism. Finally, the early perfusion of Cyclosporine A in isolated hearts decreased Casiopeinas\u2010induced dysfunction with reduction of their toxic effect. Our results suggest that heart cardiotoxicity of Casiopeinas is similar to that of Doxorubicin, involving heart mitochondrial dysfunction, loss of membrane potential, changes in energetic metabolites, and apoptosis triggered by mitochondrial permeability.<\/jats:p>","DOI":"10.1155\/2018\/8949450","type":"journal-article","created":{"date-parts":[[2018,3,25]],"date-time":"2018-03-25T23:31:45Z","timestamp":1522020705000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Ex Vivo Cardiotoxicity of Antineoplastic Casiopeinas Is Mediated through Energetic Dysfunction and Triggered Mitochondrial\u2010Dependent Apoptosis"],"prefix":"10.1155","volume":"2018","author":[{"given":"Christian","family":"Silva-Platas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar 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