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A better understanding of this syndrome may be useful to identify novel therapeutic targets because there is no specific treatment so far. Ferroptosis is an iron\u2010dependent form of regulated nonapoptotic cell death that is involved in renal injury. In this study, we investigated whether ferroptosis is associated with rhabdomyolysis\u2010mediated renal damage, and we studied the therapeutic effect of curcumin, a powerful antioxidant with renoprotective properties. Induction of rhabdomyolysis in mice increased serum creatinine levels, endothelial damage, inflammatory chemokines, and cytokine expression, alteration of redox balance (increased lipid peroxidation and decreased antioxidant defenses), and tubular cell death. Treatment with curcumin initiated before or after rhabdomyolysis induction ameliorated all these pathologic and molecular alterations. Although apoptosis or receptor\u2010interacting protein kinase (RIPK)3\u2010mediated necroptosis were activated in rhabdomyolysis, our results suggest a key role of ferroptosis. Thus, treatment with ferrostatin 1, a ferroptosis inhibitor, improved renal function in glycerol\u2010injected mice, whereas no beneficial effects were observed with the pan\u2010caspase inhibitor carbobenzoxy\u2010valyl\u2010alanyl\u2010aspartyl\u2010(\n                    <jats:italic>O<\/jats:italic>\n                    \u2010methyl)\u2010fluoromethylketone or in RIPK3\u2010deficient mice. In cultured renal tubular cells, myoglobin (Mb) induced ferroptosis\u2010sensitive cell death that was also inhibited by curcumin. Mechanistic\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies showed that curcumin reduced Mb\u2010mediated inflammation and oxidative stress by inhibiting the TLR4\/NF\u2010\u03baB axis and activating the cytoprotective enzyme heme oxygenase 1. Our findings are the first to demonstrate the involvement of ferroptosis in rhabdomyolysis\u2010associated renal damage and its sensitivity to curcumin treatment. Therefore, curcumin may be a potential therapeutic approach for patients with this syndrome.\u2014Guerrero\u2010Hue, M., Garc\u00eda\u2010Caballero, C., Palomino\u2010Antol\u00edn, A., Rubio\u2010Navarro, A., V\u00e1zquez\u2010Carballo, C., Herencia, C., Mart\u00edn\u2010Sanchez, D., Farr\u00e9\u2010Alins, V., Egea, J., Cannata, P., Praga, M., Ortiz, A., Egido, J., Sanz, A. B., Moreno, J. A. Curcumin reduces renal damage associated with rhabdomyolysis by decreasing ferroptosis\u2010mediated cell death. FASEB J. 33,8961\u20138975 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201900077r","type":"journal-article","created":{"date-parts":[[2019,4,29]],"date-time":"2019-04-29T19:46:24Z","timestamp":1556567184000},"page":"8961-8975","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":253,"title":["Curcumin reduces renal damage associated with rhabdomyolysis by decreasing ferroptosis\u2010mediated cell death"],"prefix":"10.1096","volume":"33","author":[{"given":"Melania","family":"Guerrero\u2010Hue","sequence":"first","affiliation":[{"name":"Renal, Vascular, and Diabetes Research Laboratory Fundaci\u00f3n Instituto de Investigaciones Sanitarias Fundaci\u00f3n Jim\u00e9nez D\u00edaz Aut\u00f3noma University  Madrid 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