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The G\u2010protein estrogen receptor GPER\/GPR30 mediates estrogen action as the cardioprotection under certain stressful conditions. For instance, GPER activation by the selective agonist G\u20101 reduced myocardial inflammation, improved immunosuppression, triggered pro\u2010survival signaling cascades, improved myocardial mechanical performance, and reduced infarct size after ischemia\/reperfusion (I\/R) injury. Hence, we evaluated whether ligand\u2010activated GPER may exert cardioprotection in male rats chronically treated with Dox. 1 week of G\u20101 (50\u2009\u03bcg\/kg\/day) intraperitoneal administration mitigated Dox (3\u2009mg\/kg\/day) adverse effects, as revealed by reduced TNF\u2010\u03b1, IL\u20101\u03b2, LDH, and ROS levels. Western blotting analysis of cardiac homogenates indicated that G\u20101 prevents the increase in p\u2010c\u2010jun, BAX, CTGF, iNOS, and COX2 expression induced by Dox. Moreover, the activation of GPER rescued the inhibitory action elicited by Dox on the expression of BCL2, pERK, and pAKT. TUNEL assay indicated that GPER activation may also attenuate the cardiomyocyte apoptosis upon Dox exposure. Using ex vivo Langendorff perfused heart technique, we also found an increased systolic recovery and a reduction of both infarct size and LDH levels in rats treated with G\u20101 in combination with Dox respect to animals treated with Dox alone. Accordingly, the beneficial effects induced by G\u20101 were abrogated in the presence of the GPER selective antagonist G15. These data suggest that GPER activation mitigates Dox\u2010induced cardiotoxicity, thus proposing GPER as a novel pharmacological target to limit the detrimental cardiac effects of Dox treatment. J. Cell. Physiol. 232: 1640\u20131649, 2017. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.25585","type":"journal-article","created":{"date-parts":[[2016,9,8]],"date-time":"2016-09-08T12:37:21Z","timestamp":1473338241000},"page":"1640-1649","source":"Crossref","is-referenced-by-count":49,"title":["Protective Role of GPER Agonist G\u20101 on Cardiotoxicity Induced by Doxorubicin"],"prefix":"10.1002","volume":"232","author":[{"given":"Ernestina M.","family":"De Francesco","sequence":"first","affiliation":[{"name":"Department of Pharmacy Health and Nutritional Sciences University of Calabria Rende (CS) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmine","family":"Rocca","sequence":"additional","affiliation":[{"name":"Department of Biology, Ecology, and E.S. 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