An update on the mechanisms related to cell death and toxicity of doxorubicin and the protective role of nutrients Varela López, Alfonso Battino, Maurizio Navarro Hortal, María Dolores Giampieri, Francesca Forbes Hernández, Tamara Yuliett Romero Márquez, José Manuel Collado, Ricardo Quiles Morales, José Luis Adriamycin n-3 PUFA Selenium Vitamin A Vitamin C Vitamin E This research was been partially supported by Visiting Scholar Program from the University of Granada. María D. Navarro-Hortal and José M. Romero-Márquez are FPU fellow from the Spanish Ministry of Educación y Formación Profesional. Doxorubicin (DOX), is a very effective chemotherapeutic agent against cancer whose clinical use is limited by toxicity. Different strategies have been proposed to attenuate toxicity, including combined therapy with bioactive compounds. This review update mechanisms of action and toxicity of doxorubicin and the role of nutrients like vitamins (A, C, E), minerals (selenium) and n-3 polyunsaturated fatty acids. Protective activities against DOX toxicity in liver, kidney, skin, bone marrow, testicles or brain have been reported, but these have not been evaluated for all of the reviewed nutrients. In most cases oxidation-related effects were present either, by reducing ROS levels and/or increasing antioxidant defenses. Antiapoptotic and anti-inflammatory mechanisms are also commonly reported. In some cases, interferences with autophagy and calcium homeostasis also have shown to be affected. Notwithstanding, there is a wide variety in duration and doses of treatment tested for both, compounds and DOX, which make difficult to compare the results of the studies. In spite of the reduction of DOX cardiotoxicity in health models, DOX anti-cancer activity in cancer cell lines or xenograft models usually did not result compromised when this has been evaluated. Importantly, clinical studies are needed to confirm all the observed effects. 2026-01-30T07:52:52Z 2026-01-30T07:52:52Z 2019 journal article Published version: Varela-López A, Battino M, Giampieri F, Forbes-Hernandez TY, Navarro-Hortal MD, Romero-Márquez JM, Collado R, Quiles JL. An update on the mechanisms related to cell death and toxicity of doxorubicin and the protective role of nutrients. Food and Chemical Toxicology. 2019;134:110834. https://doi.org/10.1016/j.fct.2019.110834 https://hdl.handle.net/10481/110503 10.1016/j.fct.2019.110834 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Elsevier