{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:31:19Z","timestamp":1791383479412,"version":"4.3.3"},"reference-count":72,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T00:00:00Z","timestamp":1683849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dolomite-Franchi S.p.a. (Marone, Brescia, Italy)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Doxorubicin (Doxo) is a widely prescribed drug against many malignant cancers. Unfortunately, its utility is limited by its toxicity, in particular a progressive induction of congestive heart failure. Doxo acts primarily as a mitochondrial toxin, with consequent increased production of reactive oxygen species (ROS) and attendant oxidative stress, which drives cardiac dysfunction and cell death. A diet containing a special mixture of all essential amino acids (EAAs) has been shown to increase mitochondriogenesis, and reduce oxidative stress both in skeletal muscle and heart. So, we hypothesized that such a diet could play a favorable role in preventing Doxo-induced cardiomyocyte damage. Methods: Using transmission electron microscopy, we evaluated cells\u2019 morphology and mitochondria parameters in adult mice. In addition, by immunohistochemistry, we evaluated the expression of pro-survival marker Klotho, as well as markers of necroptosis (RIP1\/3), inflammation (TNF\u03b1, IL1, NFkB), and defense against oxidative stress (SOD1, glutathione peroxidase, citrate synthase). Results: Diets with excess essential amino acids (EAAs) increased the expression of Klotho and enhanced anti-oxidative and anti-inflammatory responses, thereby promoting cell survival. Conclusion: Our results further extend the current knowledge about the cardioprotective role of EAAs and provide a novel theoretical basis for their preemptive administration to cancer patients undergoing chemotherapy to alleviate the development and severity of Doxo-induced cardiomyopathy.<\/jats:p>","DOI":"10.3390\/nu15102287","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T09:26:13Z","timestamp":1683883573000},"page":"2287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Essential Amino Acids-Rich Diet Increases Cardiomyocytes Protection in Doxorubicin-Treated Mice"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0326-0644","authenticated-orcid":false,"given":"Giovanni","family":"Corsetti","sequence":"first","affiliation":[{"name":"Division of Human Anatomy and Physiopathology, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Romano","sequence":"additional","affiliation":[{"name":"Division of Human Anatomy and Physiopathology, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evasio","family":"Pasini","sequence":"additional","affiliation":[{"name":"Italian Association of Functional Medicine, 20855 Lesmo (Milan), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziano","family":"Scarabelli","sequence":"additional","affiliation":[{"name":"Center for Heart and Vessel Preclinical Studies, St. John Hospital and Medical Center, Wayne State University, Detroit, MI 48236, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Chen-Scarabelli","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Richmond Veterans Affairs Medical Center (VAMC), Richmond, VA 23249, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0445-3106","authenticated-orcid":false,"given":"Francesco S.","family":"Dioguardi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Cagliari, 09042 Monserrato (Cagliari), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,12]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Anthracyclines in the treatment of cancer: An overview","volume":"54","author":"Hortobagyi","year":"1997","journal-title":"Drugs"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1006\/gyno.2001.6355","article-title":"Anthracyclines in the treatment of gynecologic malignancies","volume":"85","author":"Maluf","year":"2002","journal-title":"Gynecol. 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