Oxidative stress in the pathogenesis of skin disease
Oxidative stress in the pathogenesis of skin disease
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DOI：
10.1038/sj.jid.5700340
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发表时间：
2006-12-01
影响因子：
6.5
通讯作者：
Athar, Mohammad
中科院分区：
文献类型：
--
作者：
Bickers, David R.;Athar, Mohammad
皮肤是人体最大的器官，作为一个重要的环境界面，提供了一个保护性的信封，这是至关重要的稳态。另一方面，皮肤是能够改变其结构和功能的广谱物理（即UV辐射）和化学（异生素）试剂的毒性损伤的主要目标。许多环境污染物本身就是氧化剂，或者直接或间接催化活性氧（ROS）的产生。ROS被认为激活增殖和细胞存活信号传导，其可以改变可能参与许多皮肤病症（包括光敏性疾病和某些类型的皮肤恶性肿瘤）的发病机制的凋亡途径。ROS主要通过驱动几个重要的分子途径发挥作用，这些分子途径在包括缺血再灌注损伤、动脉粥样硬化和炎症反应在内的多种病理过程中发挥重要作用。皮肤具有一系列的防御机制，与毒物相互作用，以消除其有害影响。这些包括非酶和酶分子，作为有效的抗氧化剂或氧化剂降解系统。不幸的是，这些稳态防御虽然非常有效，但能力有限，并且可能被淹没，从而导致皮肤中ROS增加，这可能促进皮肤病的发展。预防或治疗这些ROS介导的病症的一种方法是基于施用各种抗氧化剂以努力恢复体内平衡。尽管许多抗氧化剂在细胞培养系统和氧化损伤的动物模型中显示出实质性的功效，但其在人群中的有益作用的明确证实已被证明是难以捉摸的。
Skin is the largest body organ that serves as an important environmental interface providing a protective envelope that is crucial for homeostasis. On the other hand, the skin is a major target for toxic insult by a broad spectrum of physical (i.e. UV radiation) and chemical (xenobiotic) agents that are capable of altering its structure and function. Many environmental pollutants are either themselves oxidants or catalyze the production of reactive oxygen species (ROS) directly or indirectly. ROS are believed to activate proliferative and cell survival signaling that can alter apoptotic pathways that may be involved in the pathogenesis of a number of skin disorders including photosensitivity diseases and some types of cutaneous malignancy. ROS act largely by driving several important molecular pathways that play important roles in diverse pathologic processes including ischemia-reperfusion injury, atherosclerosis, and inflammatory responses. The skin possesses an array of defense mechanisms that interact with toxicants to obviate their deleterious effect. These include nonenzymatic and enzymatic molecules that function as potent antioxidnts or oxidant-degrading systems. Unfortunately, these homeostatic defenses, although highly effective, have limited capacity and can be overwhelmed thereby leading to increased ROS in the skin that can foster the development of dermatological diseases. One approach to preventing or treating these ROS-mediated disorders is based on the administration of various antioxidants in an effort to restore homeostasis. Although many antioxidants have shown substantive efficacy in cell culture systems and in animal models of oxidant injury, unequivocal confirmation of their beneficial effects in human populations has proven elusive.