Mechanisms and Protective Strategies in Cognitive Impairment Induced by Combination of Doxorubicin and Cyclophosphamide

Nada K. Gamal, Reem Elnaga, Mina Y. George
{"title":"Mechanisms and Protective Strategies in Cognitive Impairment Induced by Combination of Doxorubicin and Cyclophosphamide","authors":"Nada K. Gamal, Reem Elnaga, Mina Y. George","doi":"10.21608/aps.2024.260718.1154","DOIUrl":null,"url":null,"abstract":"The introduction of combination chemotherapy raised the survival rate of cancer patients. However, it is associated with chemotherapy-induced cognitive impairment, often referred to as \"chemobrain\", which is a distressing adverse effect of cancer treatment. Doxorubicin and cyclophosphamide, two widely used chemotherapeutic agents in the treatment of various malignancies, have been shown to induce cognitive dysfunction. This review explores the underlying mechanisms that contribute to the chemobrain induced by doxorubicin and cyclophosphamide combination therapy, shedding light on oxidative stress, inflammation, neurotransmitter dysregulation, and neuroinflammation. Studies have shown that chemobrain is associated with activated inflammation and oxidative damage in the hippocampus. We also delve into the molecular pathways activated by doxorubicin and cyclophosphamide, such as the extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) signaling pathways, which are implicated in cognitive dysfunction. Additionally, this article explores protective approaches, including antioxidants like L-Carnitine, polyphenolic-rich compounds from Thunbergia erecta , and N-acetylcysteine, offering potential solutions for alleviating doxorubicin and cyclophosphamide-induced chemobrain. Notably, these protective agents, although promising in pre-clinical models, await clinical investigation. Therefore, there is a gap in data to support the application of any neuroprotective medication in a clinical context. Thus, clinical trials are necessary to assess their therapeutic potential. In conclusion, this review integrates data from diverse studies to elucidate the mechanisms and suggests potential protective strategies, offering insights for researchers seeking to alleviate cognitive challenges in doxorubicin and cyclophosphamide-treated cancer patients.","PeriodicalId":8314,"journal":{"name":"Archives of Pharmaceutical Sciences Ain Shams University","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Pharmaceutical Sciences Ain Shams University","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.21608/aps.2024.260718.1154","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

The introduction of combination chemotherapy raised the survival rate of cancer patients. However, it is associated with chemotherapy-induced cognitive impairment, often referred to as "chemobrain", which is a distressing adverse effect of cancer treatment. Doxorubicin and cyclophosphamide, two widely used chemotherapeutic agents in the treatment of various malignancies, have been shown to induce cognitive dysfunction. This review explores the underlying mechanisms that contribute to the chemobrain induced by doxorubicin and cyclophosphamide combination therapy, shedding light on oxidative stress, inflammation, neurotransmitter dysregulation, and neuroinflammation. Studies have shown that chemobrain is associated with activated inflammation and oxidative damage in the hippocampus. We also delve into the molecular pathways activated by doxorubicin and cyclophosphamide, such as the extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) signaling pathways, which are implicated in cognitive dysfunction. Additionally, this article explores protective approaches, including antioxidants like L-Carnitine, polyphenolic-rich compounds from Thunbergia erecta , and N-acetylcysteine, offering potential solutions for alleviating doxorubicin and cyclophosphamide-induced chemobrain. Notably, these protective agents, although promising in pre-clinical models, await clinical investigation. Therefore, there is a gap in data to support the application of any neuroprotective medication in a clinical context. Thus, clinical trials are necessary to assess their therapeutic potential. In conclusion, this review integrates data from diverse studies to elucidate the mechanisms and suggests potential protective strategies, offering insights for researchers seeking to alleviate cognitive challenges in doxorubicin and cyclophosphamide-treated cancer patients.
多柔比星和环磷酰胺联合疗法诱发认知障碍的机制和保护策略
联合化疗的引入提高了癌症患者的生存率。然而,它与化疗引起的认知障碍(通常称为 "化疗脑")有关,这是癌症治疗中令人苦恼的不良反应。多柔比星和环磷酰胺这两种广泛用于治疗各种恶性肿瘤的化疗药物已被证实会诱发认知功能障碍。这篇综述探讨了多柔比星和环磷酰胺联合疗法诱发化疗脑的潜在机制,揭示了氧化应激、炎症、神经递质失调和神经炎症。研究表明,化疗脑与海马中激活的炎症和氧化损伤有关。我们还深入研究了由多柔比星和环磷酰胺激活的分子通路,如细胞外信号调节激酶(ERK)和蛋白激酶 B(AKT)信号通路,这些通路与认知功能障碍有关。此外,本文还探讨了保护性方法,包括抗氧化剂(如左旋肉碱)、来自直立蓟的富含多酚的化合物和 N-乙酰半胱氨酸,它们为缓解多柔比星和环磷酰胺诱导的化疗脑提供了潜在的解决方案。值得注意的是,这些保护剂虽然在临床前模型中很有前景,但仍有待临床研究。因此,在临床应用任何神经保护药物方面还存在数据缺口。因此,有必要进行临床试验以评估其治疗潜力。总之,本综述整合了不同研究的数据,阐明了其机制并提出了潜在的保护策略,为研究人员减轻多柔比星和环磷酰胺治疗的癌症患者的认知挑战提供了启示。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
15
审稿时长
12 weeks
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信