Targeting oxidative stress in disease: promise and limitations of antioxidant therapy.

文献信息

DOI	10.1038/s41573-021-00233-1
PMID	34194012
期刊	Nature reviews. Drug discovery
影响因子	101.8
JCR 分区	Q1
发表年份	2021
被引次数	1004
关键词	氧化应激, 抗氧化治疗, 疾病机制, 红氧信号, 药理学
文献类型	Journal Article, Research Support, N.I.H., Extramural, Review
ISSN	1474-1776
页码	689-709
期号	20(9)
作者	Henry Jay Forman, Hongqiao Zhang

一句话小结

本研究探讨了氧化应激在多种疾病中的作用及其与抗氧化剂疗效的关系，强调深入理解抗氧化剂的作用机制和应用时机的重要性。通过回顾相关文献，提出了增强抗氧化防御的策略，为未来药理学研究提供了新的思路和方向。

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氧化应激 · 抗氧化治疗 · 疾病机制 · 红氧信号 · 药理学

摘要

氧化应激是许多疾病的一个组成部分，包括动脉粥样硬化、慢性阻塞性肺疾病、阿尔茨海默病和癌症。尽管许多被评估为抗氧化剂的小分子在临床前研究中显示出了治疗潜力，但临床试验结果却令人失望。更深入地理解抗氧化剂的作用机制以及其有效的时机和地点，可能为实现更高的药理学成功提供合理的途径。在这里，我们回顾了氧化应激、氧化还原信号传导与疾病之间的关系，氧化应激如何促进病理的发展，抗氧化防御的工作机制，限制其有效性的因素，以及如何通过生理信号、饮食成分和潜在的药物干预来增强抗氧化防御。

英文摘要

Oxidative stress is a component of many diseases, including atherosclerosis, chronic obstructive pulmonary disease, Alzheimer disease and cancer. Although numerous small molecules evaluated as antioxidants have exhibited therapeutic potential in preclinical studies, clinical trial results have been disappointing. A greater understanding of the mechanisms through which antioxidants act and where and when they are effective may provide a rational approach that leads to greater pharmacological success. Here, we review the relationships between oxidative stress, redox signalling and disease, the mechanisms through which oxidative stress can contribute to pathology, how antioxidant defences work, what limits their effectiveness and how antioxidant defences can be increased through physiological signalling, dietary components and potential pharmaceutical intervention.

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主要研究问题

核心洞察

研究背景和目的

氧化应激是许多疾病的一个重要组成部分，包括动脉粥样硬化、慢性阻塞性肺病、阿尔茨海默病和癌症。尽管许多小分子抗氧化剂在前临床研究中显示出治疗潜力，但临床试验结果却令人失望。本文旨在探讨氧化应激、红氧信号传导与疾病之间的关系，分析抗氧化防御机制及其局限性，并提出可能的药物干预策略。

主要方法/材料/实验设计

本文通过文献回顾的方式总结了氧化应激的机制及其在疾病中的作用，特别关注抗氧化防御的生理信号、饮食成分及潜在的药物干预。以下是研究的技术路线图：

关键结果和发现

氧化应激的机制：氧化应激通过产生反应性氧种（ROS）直接氧化大分子（如脂质、蛋白质和DNA），导致细胞功能异常和死亡。
红氧信号传导：在生理条件下，H2O2作为第二信使参与细胞信号传导，但在氧化应激中，H2O2的非生理产生会导致信号失调。
抗氧化防御的局限性：小分子抗氧化剂在细胞内的清除能力微不足道，主要的抗氧化防御依赖于抗氧化酶。
潜在的治疗机会：通过减少氧化物的产生、抑制下游信号传导以及增加抗氧化酶和其底物，可以改善治疗效果。

主要结论/意义/创新性

尽管抗氧化治疗的潜力巨大，但实际应用中面临许多挑战。理解氧化应激在疾病中的具体作用，以及抗氧化防御的局限性，可以帮助开发更有效的治疗策略。特别是通过药物增强内源性抗氧化酶的活性和底物的供给，将是未来研究的重点。

研究局限性和未来方向

研究局限性：目前对氧化应激在多种疾病中的作用尚不完全了解，特别是在氧化应激作为病理的次要贡献者时，其治疗效果可能有限。
未来方向：需要进一步研究如何在临床中有效激活NRF2信号通路以增强抗氧化防御，同时评估长期使用抗氧化剂的潜在副作用。探索新的药物形式和给药策略以提高生物利用度，也是未来研究的关键。

参考文献

Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress. - Helmut Sies - Redox biology (2017)
Oxidative Stress. - Helmut Sies;Carsten Berndt;Dean P Jones - Annual review of biochemistry (2017)
Free radicals and antioxidants in normal physiological functions and human disease. - Marian Valko;Dieter Leibfritz;Jan Moncol;Mark T D Cronin;Milan Mazur;Joshua Telser - The international journal of biochemistry & cell biology (2007)
How do nutritional antioxidants really work: nucleophilic tone and para-hormesis versus free radical scavenging in vivo. - Henry J Forman;Kelvin J A Davies;Fulvio Ursini - Free radical biology & medicine (2014)
Strategies of antioxidant defense. - H Sies - European journal of biochemistry (1993)
Signaling functions of reactive oxygen species. - Henry Jay Forman;Matilde Maiorino;Fulvio Ursini - Biochemistry (2010)
Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. - Joseph L Evans;Ira D Goldfine;Betty A Maddux;Gerold M Grodsky - Endocrine reviews (2002)
The role of O2.- in the production of HO.: in vitro and in vivo. - S I Liochev;I Fridovich - Free radical biology & medicine (1994)
Aconitases: Non-redox Iron-Sulfur Proteins Sensitive to Reactive Species. - Laura Castro;Verónica Tórtora;Santiago Mansilla;Rafael Radi - Accounts of chemical research (2019)
4-hydroxynonenal-mediated signaling and aging. - Hongqiao Zhang;Henry Jay Forman - Free radical biology & medicine (2017)

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... (994 更多篇文献)

Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. ​

文献信息 ​

一句话小结 ​

在麦伴科研 (maltsci.com) 搜索更多文献 ​

摘要 ​

英文摘要 ​

麦伴智能科研服务 ​

主要研究问题 ​

核心洞察 ​

研究背景和目的 ​

主要方法/材料/实验设计 ​

关键结果和发现 ​

主要结论/意义/创新性 ​

研究局限性和未来方向 ​

参考文献 ​

引用本文的文献 ​