Astaxanthin: A novel potential treatment for oxidative stress and inflammation in cardiovascular disease
Astaxanthin: A novel potential treatment for oxidative stress and inflammation in cardiovascular disease
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DOI：
10.1016/j.amjcard.2008.02.010
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发表时间：
2008-05-22
影响因子：
2.8
通讯作者：
Campbell, Charles L.
中科院分区：
文献类型：
--
作者：
Pashkow, Fredric J.;Watumull, David G.;Campbell, Charles L.
氧化应激和炎症与心血管疾病(CVD)的几种不同表现有关。它们在一定程度上是由于激活转录信使的活性氧簇(ROS)和活性氮簇(RNS)的过度产生而产生的，这些转录信使如核因子-kappaB，确实有助于内皮功能障碍、动脉粥样硬化的发生和发展，缺血再灌注后的不可逆转损伤，甚至心律失常，如房颤。尽管氧化应激和心血管疾病之间存在这种联系，但目前还没有公认的治疗干预措施来满足这一重要的未得到满足的需求。根据流行病学、饮食和活体动物模型数据，通过ROS/RNS猝灭或自由基链断裂提供广泛的“上游”途径的抗氧化剂似乎是一种合适的治疗选择。然而，人体临床试验使用了几种不同的知名药物，如。像维生素E和β-胡萝卜素一样，一直令人失望。这是否意味着抗氧化剂作为一个类别是无效的，或者更确切地说，“正确的”化合物(S)还没有找到，它们的作用机制还没有被理解，它们的适当靶向和剂量还没有确定？自然界开发的一大类有效的天然抗氧化剂--含氧类胡萝卜素(叶黄素)--在其自然形式下表现出了实用价值，但到目前为止一直没有被开发为成功的靶向治疗剂。本文描述了这类新的抗氧化剂的作用机制，并回顾了它们的临床前发展。来自多个物种的结果支持原型化合物虾青素的抗氧化/抗炎特性，使其成为作为心血管氧化应激和炎症的治疗药物开发的合适候选药物。(C)2008 Elsevier Inc.保留所有权利。
Oxidative stress and inflammation are implicated in several different manifestations of cardiovascular disease (CVD). They are generated, in part, from the overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that activate transcriptional messengers, such as nuclear factor-kappa B, tangibly contributing to endothelial dysfunction, the initiation and progression of atherosclerosis, irreversible damage after ischemic reperfusion, and even arrhythmia, such as atrial fibrillation. Despite this connection between oxidative stress and CVD, there are currently no recognized therapeutic interventions to address this important unmet need. Antioxidants that provide a broad, "upstream" approach via ROS/RNS quenching or free radical chain breaking seem an appropriate therapeutic option based on epidemiologic, dietary, and in vivo animal model data. However, human clinical trials with several different well-known agents, such. as vitamin E and beta-carotene, have been disappointing. Does this mean antioxidants as a class are ineffective, or rather that the "right" compound(s) have yet to be found, their mechanisms of action understood, and their appropriate targeting and dosages determined? A large class of potent naturally-occurring antioxidants exploited by nature-the oxygenated carotenoids (xanthophylls)-have demonstrated utility in their natural form but have eluded development as successful targeted therapeutic agents up to the present time. This article characterizes the mechanism by which this novel group of antioxidants function and reviews their preclinical development. Results from multiple species support the antioxidant/anti-inflammatory properties of the prototype compound, astaxanthin, establishing it as an appropriate candidate for development as a therapeutic agent for cardiovascular oxidative stress and inflammation. (C) 2008 Elsevier Inc. All rights reserved.