摘要
氧化应激与许多疾病有关,包括癌症、退行性疾病,抗氧化剂在这些疾病的治疗中有可能具有治疗价值。这篇综述中,我们将抗氧化剂发挥他们活性的不同、直接和间接机制进行了分类。这些机制包括清除和金属螯合效用,模仿抗氧化酶或者他们的上调表达,Nrf2的激活,增加去乙酰化酶的活性及抑制助氧化酶活性等。对最近发现的研究最为频繁的抗氧化剂包括多酚类、硫羟酸类、自旋捕获剂、拟SOD剂、血红素加氧酶-1诱导物和一氧化氮合成酶、Nrf2催化剂、NADPH氧化酶抑制剂和草药补充剂进行了总结。此外,对临床上用于其他药理用途的药物包括血管紧张素转换酶抑制剂和他汀类药物的抗氧化作用进行了讨论。对抗氧化剂的成本高效益和副作用也进行了评价。因为抗氧化治疗在许多情况下都会失败,所以我们对可以解释这些不同类别缺陷的原因进行了分类。也描述了抗氧化治疗的新方法,包括线粒体靶向药物、氧化基因治疗和提高细胞吸收和亚细胞间隔定位修改的方法。最后,对抗氧化治疗的缺点----“阴影”和抗氧化治疗的积极效果----“光明”进行了阐述。结果表明,如果我们从失败中吸取经验教训,为具有较高潜力的药物投资并利用新颖的新兴方法,抗氧化剂针对一些特定的与氧化应激相关的疾病可能具有相对的优势。
关键词: 抗氧化剂,线粒体功能障碍,神经退行性疾病,Nrf2,NOX
Current Drug Targets
Title:Pharmacological Applications of Antioxidants: Lights and Shadows
Volume: 15 Issue: 13
Author(s): Luciano Saso and Omidreza Firuzi
Affiliation:
关键词: 抗氧化剂,线粒体功能障碍,神经退行性疾病,Nrf2,NOX
摘要: Oxidative stress is linked with many pathologies ranging from cancer to neurodegenerative disorders and antioxidants have presumably therapeutic value in such diseases. In this review, we categorize different direct and indirect mechanisms by which antioxidants exert their action. These include scavenging and metal chelating effects, mimicking the antioxidant enzymes or upregulation of their expression, activation of nuclear factor erythroid 2-related factor 2 (Nrf2), increasing the activity of sirtuins and inhibition of pro-oxidant enzymes among others. Recent findings on the most frequently investigated antioxidants including polyphenolics, thiolics, spin trapping agents, SOD mimetics, inducers of heme oxygenase-1 and nitric oxide synthase, activators of Nrf2, NADPH oxidase inhibitors and herbal supplements are summarized. Furthermore, the antioxidant effects of drugs that are clinically used for other pharmacological purposes including ACE inhibitors and statins are discussed. Cost-effectiveness and adverse effects of antioxidants are also evaluated. Since antioxidant therapy has failed in many instances, we have classified the reasons that may explain these shortcomings in different categories. Novel approaches to antioxidant therapy, that include mitochondria-targeting drugs, antioxidant gene therapy and approaches for improvement of cell uptake and alteration of subcellular compartment localization are also described. In the end, “shadows” that are shortcomings of antioxidant therapy as well as “lights” that include positive outcomes are addressed. It is concluded that if we learn from failures, invest on agents with higher potential and take advantage of novel emerging approaches, antioxidants could be an asset for the management of certain carefully chosen oxidative stress-related diseases.
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Luciano Saso and Firuzi Omidreza, Pharmacological Applications of Antioxidants: Lights and Shadows, Current Drug Targets 2014; 15 (13) . https://dx.doi.org/10.2174/1389450115666141024113925
DOI https://dx.doi.org/10.2174/1389450115666141024113925 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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