Serini Simona, Calviello Gabriella
Department of Translational Medicine and Surgery, Section of General Pathology, School of Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo F. Vito, 00168 Rome, Italy.
Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo F. Vito, 00168 Rome, Italy.
Antioxidants (Basel). 2024 Apr 18;13(4):486. doi: 10.3390/antiox13040486.
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.
化疗引起的认知障碍或“化疗脑”是化疗常见的长期并发症，也是危害较大的并发症之一。迄今为止，大多数旨在确定抗肿瘤化疗药物所致认知功能障碍的研究都聚焦于使用蒽环类药物进行的治疗，这类药物常用于乳腺癌患者，而该群体在治疗后有很高的长期存活可能性，因此也有很高的发生化疗脑的可能性。在过去几年里，人们探索了不同的可能策略来预防或减轻由蒽环类药物阿霉素（DOX）引起的化疗脑，已知DOX会促进氧化应激和炎症，而这两者与这种脑功能障碍的发生密切相关。在此，我们对过去几年的临床前研究结果进行了批判性分析，这些研究评估了酚类化合物（PheCs）抑制DOX诱导的化疗脑的潜力，酚类化合物是一大类具有强大抗氧化和抗炎活性的天然产物。已表明，几种不同类别的PheCs能够逆转DOX诱导的脑形态损伤以及与学习、记忆和探索行为相关的缺陷。我们分析了其中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发展方向。
