Chemotherapy-induced cognitive impairment or “chemobrain” is a prevalent long-term complication of chemotherapy and one of the more devastating. Most of the studies performed so far to identify the cognitive dysfunctions induced by antineoplastic chemotherapies have been focused on treatment with anthracyclines, frequently administered to breast cancer patients, a population that, after treatment, shows a high possibility of long survival and, consequently, of chemobrain development. In the last few years, different possible strategies have been explored to prevent or reduce chemobrain induced by the anthracycline doxorubicin (DOX), known to promote oxidative stress and inflammation, which have been strongly implicated in the development of this brain dysfunction. Here, we have critically analyzed the results of the preclinical studies from the last few years that have evaluated the potential of phenolic compounds (PheCs), a large class of natural products able to exert powerful antioxidant and anti-inflammatory activities, in inhibiting DOX-induced chemobrain. Several PheCs belonging to different classes have been shown to be able to revert DOX-induced brain morphological damages and deficits associated with learning, memory, and exploratory behavior. We have analyzed the biological and molecular mechanisms implicated and suggested possible future perspectives in this research area.

中文翻译：

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天然酚类化合物对抗阿霉素诱导的化学脑的潜力：涉及的生物和分子机制

化疗引起的认知障碍或“化疗脑”是化疗常见的长期并发症，也是最具破坏性的并发症之一。迄今为止，为确定抗肿瘤化疗引起的认知功能障碍而进行的大多数研究都集中在蒽环类药物的治疗上，这些药物经常用于乳腺癌患者，这些患者在治疗后表现出长期生存的可能性很高，因此，化学脑发育。在过去的几年中，人们探索了不同的可能策略来预防或减少蒽环类阿霉素（DOX）诱导的化学脑，已知该药物会促进氧化应激和炎症，而这与这种脑功能障碍的发展密切相关。在这里，我们批判性地分析了过去几年的临床前研究结果，这些研究评估了酚类化合物 (PheC) 的潜力，这是一大类能够发挥强大的抗氧化和抗炎活性的天然产物，在抑制 DOX-诱导化学脑。几种属于不同类别的 PheC 已被证明能够恢复 DOX 引起的大脑形态损伤以及与学习、记忆和探索行为相关的缺陷。我们分析了所涉及的生物学和分子机制，并提出了该研究领域未来可能的前景。