Department of Physiology, Institute of Nutrition and Food Technology ''José Mataix", Biomedical Research Centre, University of Granada, 18071, Granada, Spain.
Dipartimento di Scienze Cliniche Specialistiche Ed Odontostomatologiche (DISCO)-Sez, Biochimica, Facoltà di Medicina, Università Politecnica Delle Marche, 60131, Ancona, Italy; Nutrition and Food Science Group. Department of Analytical and Food Chemistry, CITACA, CACTI, University of Vigo, Vigo, Spain; International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang, China.
Food Chem Toxicol. 2019 Dec;134:110834. doi: 10.1016/j.fct.2019.110834. Epub 2019 Sep 29.
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.
多柔比星（DOX）是一种非常有效的抗癌化疗药物，但由于其毒性限制了其临床应用。人们提出了不同的策略来减轻其毒性，包括与生物活性化合物联合治疗。本综述更新了多柔比星的作用机制和毒性，以及维生素（A、C、E）、矿物质（硒）和 n-3 多不饱和脂肪酸等营养素的作用。已经报道了它们在肝脏、肾脏、皮肤、骨髓、睾丸或大脑中对 DOX 毒性的保护作用，但尚未对所有综述营养素进行评估。在大多数情况下，氧化相关的效应都存在，要么通过降低 ROS 水平和/或增加抗氧化防御，要么通过抑制细胞凋亡和炎症反应。在某些情况下，自噬和钙稳态的干扰也受到影响。尽管如此，对于化合物和 DOX 的测试，无论是治疗持续时间还是剂量都有很大的差异，这使得很难比较研究结果。尽管在健康模型中降低了 DOX 的心脏毒性，但在评估时，DOX 在癌细胞系或异种移植模型中的抗癌活性通常不会受到影响。重要的是，需要进行临床研究来证实所有观察到的效果。
