Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada.
Med Sci Monit. 2010 Jan;16(1):RA9-24.
Reactive oxygen species (ROS) have deleterious or beneficial effects; this dual nature of ROS means that ROS act as intracellular signaling molecules and as defense mechanisms against micro-organisms. An overproduction of ROS results in oxidative stress, a deleterious process that damages cell structures, including lipids, proteins, and DNA. Oxidative stress plays a major role in various human disease states, including endocrine dysfunction. As a safeguard against oxidative stress, several endogenous nonenzymatic and enzymatic antioxidant systems exist. Antioxidants can delay or prevent oxidative stress and are widely used in the hope of maintaining health and preventing diseases. Although early studies suggested that antioxidant supplements promoted health, later clinical trials revealed that it may not be true in all cases. In this article, we provide a brief review of the pathophysiologic aspects of oxidative stress in a number of the most commonly human endocrionopathies (diabetes, male and female infertility and thyroid diseases) and review the therapeutic potentials of existing antioxidant strategies. We focus on human clinical trials and discuss the implications of their results. Based on the data reported so far, we conclude that the results reported challenge us to design better antioxidant trials in future, with a particular emphasis on identifying 1) appropriate doses 2) selecting the right populations 3) treating for optimal durations and 4) specific intracellular targeting mechanisms.
活性氧(ROS)具有有害或有益的影响;ROS 的这种双重性质意味着 ROS 作为细胞内信号分子和抵御微生物的防御机制发挥作用。ROS 的过度产生会导致氧化应激,这是一种有害的过程,会损害细胞结构,包括脂质、蛋白质和 DNA。氧化应激在各种人类疾病状态中起着重要作用,包括内分泌功能障碍。作为对氧化应激的一种保护措施,存在几种内源性非酶和酶抗氧化系统。抗氧化剂可以延迟或预防氧化应激,并且被广泛使用,以期保持健康和预防疾病。尽管早期的研究表明抗氧化剂补充剂促进了健康,但后来的临床试验表明,在所有情况下并非如此。在本文中,我们简要回顾了几种最常见的人类内分泌疾病(糖尿病、男性和女性不育以及甲状腺疾病)中氧化应激的病理生理方面,并回顾了现有的抗氧化策略的治疗潜力。我们重点关注人类临床试验,并讨论其结果的意义。基于迄今为止报告的数据,我们得出的结论是,报告的结果促使我们在未来设计更好的抗氧化试验,特别强调确定 1)适当的剂量 2)选择合适的人群 3)治疗最佳持续时间和 4)特定的细胞内靶向机制。