Reactive Carbonyl Species Scavengers-Novel Therapeutic Approaches for Chronic Diseases.
Reactive Carbonyl Species Scavengers-Novel Therapeutic Approaches for Chronic Diseases.
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DOI：
10.1007/s40495-017-0081-6
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发表时间：
2017-04
影响因子：
--
通讯作者：
Zhang LS
中科院分区：
文献类型：
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作者：
Davies SS;Zhang LS
总结最近支持使用活性羰基清除剂预防和治疗疾病的证据。新开发的2-氨甲基苯酚类清除剂在临床前试验中显示出巨大的前景，用于许多不同的疾病，包括神经退行性疾病和心血管疾病。此外，基于硫醇和咪唑的清除剂的新研究发现了化疗药物的连续治疗之外的新应用。由细胞和组织产生的活性氧（ROS）作为信号分子和细胞毒性剂来防御病原体，但ROS也会对重要的细胞成分造成附带损害。细胞膜中磷脂的多不饱和脂肪酰基链特别容易受到ROS的破坏性过氧化作用的影响。有证据表明，这些过氧化脂质分解为活性羰基物质在许多慢性疾病中起着关键作用。消除活性氧诱导的反应性羰基物质形成的抗氧化剂也消除了正常的活性氧信号传导，从而产生有益和不利的功能效应。活性二羰基物质的清除剂的使用代表了一种替代的治疗策略，以潜在地减轻ROS的不良作用，而不消除ROS的正常信号传导。在这篇综述中，我们专注于三类反应性羰基物质清除剂：基于巯基的清除剂（2-巯基乙磺酸盐和氨磷汀），咪唑类清除剂（肌肽及其类似物），和2-氨基甲基苯酚类清除剂（吡哆胺，2-羟基苄胺，和5 '-O-戊基-吡哆胺），无论是正在进行临床前研究，推进到临床试验，或已经在临床使用。
To summarize recent evidence supporting the use of reactive carbonyl species scavengers in the prevention and treatment of disease. The newly developed 2-aminomethylphenol class of scavengers shows great promise in preclinical trials for a number of diverse conditions including neurodegenerative diseases and cardiovascular disease. In addition, new studies with the thiol-based and imidazole-based scavengers have found new applications outside of adjunctive therapy for chemotherapeutics. Reactive oxygen species (ROS) generated by cells and tissues act as signaling molecules and as cytotoxic agents to defend against pathogens, but ROS also cause collateral damage to vital cellular components. The polyunsaturated fatty acyl chains of phospholipids in the cell membranes are particularly vulnerable to damaging peroxidation by ROS. Evidence suggests that the breakdown of these peroxidized lipids to reactive carbonyls species plays a critical role in many chronic diseases. Antioxidants that abrogate ROS-induced formation of reactive carbonyl species also abrogate normal ROS signaling and thus exert both beneficial and adverse functional effects. The use of scavengers of reactive dicarbonyl species represent an alternative therapeutic strategy to potentially mitigate the adverse effects of ROS without abrogating normal signaling by ROS. In this review, we focus on three classes of reactive carbonyl species scavengers: thiol-based scavengers (2-mercaptoethanesulfonate and amifostine), imidazole-based scavengers (carnosine and its analogs), and 2-aminomethylphenols-based scavengers (pyridoxamine, 2-hydroxybenzylamine, and 5’-O-pentyl-pyridoxamine) that are either undergoing pre-clinical studies, advancing to clinical trials, or are already in clinical use.