Mechanistic insights into the direct antioxidant effects of estrogens
Mechanistic insights into the direct antioxidant effects of estrogens
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DOI：
10.1002/ddr.20050
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发表时间：
2005-10-01
影响因子：
3.8
通讯作者：
Simpkins, JW
中科院分区：
文献类型：
--
作者：
Prokai, L;Prokai-Tatrai, K;Simpkins, JW
雌激素清除自由基被认为是其非基因组（雌激素受体非依赖性）细胞保护机制之一。这种活性与这些分子结构中酚A环的存在有关，因此使它们成为称为酚类抗氧化剂的化合物类别的成员。雌激素的直接氧自由基清除被认为可以中断自由基链反应，如脂质过氧化，并防止自由基诱导的生物大分子，如DNA和蛋白质的氧化损伤。这些抗氧化作用不仅由对活性氧或活性氮的化学反应性决定，而且还由雌激素在生物微环境中的流动性和/或分布以及雌激素衍生自由基的命运决定。最近的研究结果强调了旨在了解潜在化学机制细节的调查的重要性，特别是关注雌激素神经保护作用。这些基础研究促进了以前未被认识的雌激素抗氧化循环的发现，其中雌激素衍生的醌醇是关键中间体。此外，在动物模型中使用这些醌醇作为前药，与直接用雌性化激素治疗相比，副作用显著减少。
Free-radical scavenging by estrogens has been implicated as one of their non-genomic (estrogen-receptor independent) mechanisms of cytoprotection. This activity is associated with the presence of the phenolic A-ring in the structure of these molecules, thus rendering them members of the class of compounds called phenolic antioxidants. Direct oxyradical-scavenging by estrogens has been thought to cause interruption of free-radical chain reactions such as lipid peroxidation, and to prevent free-radical induced oxidative damage to biological macromolecules such as DNA and proteins. These antioxidant effects are determined not only by chemical reactivities toward reactive oxygen or reactive nitrogen species, but also by the mobility and/or distribution of estrogens in the biological microenvironment and by the fate of the estrogen-derived radicals. Recent results have highlighted the importance of investigations aimed at understanding mechanistic details of the underlying chemistry, especially with a focus on estrogen neuroprotection. Such fundamental studies have facilitated the discovery of a previously unrecognized antioxidant cycle for estrogens in which estrogen-derived quinols are key intermediates. Additionally, the use of these quinols as prodrugs in animal models has revealed a significant reduction of side effects compared to treatment directly with the feminizing hormones.