Rego A C, Santos M S, Oliveira C R
Center for Neurosciences of Coimbra, University of Coimbra, Portugal.
Free Radic Biol Med. 1999 Jun;26(11-12):1405-17. doi: 10.1016/s0891-5849(98)00337-2.
A role for the antioxidants vitamin E and idebenone in decreasing retinal cell injury, after metabolic inhibition induced by chemical ischemia and hypoglycemia, was investigated and compared with oxidative stress conditions. Preincubation of the antioxidants, vitamin E (20 microM) and idebenone (10 microM), effectively protected from retinal cell injury after oxidative stress or hypoglycemia, whereas the protection afforded after postincubation of both antioxidants was decreased. Delayed retinal cell damage, mediated by chemical ischemia, was attenuated at 10 or 12 h postischemia, only after exposure to the antioxidants during all the experimental procedure. An antagonist of the N-methyl-D-aspartate (NMDA) receptors, an inhibitor of nitric oxide synthase (NOS) or a blocker of L-type Ca2+ channels were ineffective in reducing cell injury induced by chemical ischemia, hypoglycemia or oxidative stress. Oxidative stress and hypoglycemia increased (about 1.2-fold) significantly the fluorescence of the probe DCFH2-DA, that is indicative of intracellular ROS formation. Free radical generation detected with the probe dihydrorhodamine 123 (DHR 123) was enhanced after oxidative stress, chemical ischemia or hypoglycemia (about 2-fold). Nevertheless, the antioxidants vitamin E or idebenone were ineffective against intracellular ROS generation. Cellular energy charge decreased greatly after chemical ischemia, was moderately affected after hypoglycemia, but no significant changes were observed after oxidative stress. Preincubation with vitamin E prevented the changes in energy charge upon 6 h posthypoglycemia. We can conclude that irreversible changes occurring during chemical ischemia mainly reflect the alterations taking place at the ischemic core, whereas hypoglycemia situations may reflect changes occurring at the penumbra area, whereby vitamin E or idebenone may help to increase cell survival, exerting a beneficial neuroprotective effect.
研究了抗氧化剂维生素E和艾地苯醌在减轻化学性缺血和低血糖诱导的代谢抑制后视网膜细胞损伤中的作用，并与氧化应激条件进行了比较。抗氧化剂维生素E（20微摩尔）和艾地苯醌（10微摩尔）预孵育可有效保护视网膜细胞免受氧化应激或低血糖后的损伤，而两种抗氧化剂后孵育所提供的保护作用则有所降低。仅在整个实验过程中暴露于抗氧化剂后，化学性缺血介导的延迟性视网膜细胞损伤在缺血后10或12小时减弱。N-甲基-D-天冬氨酸（NMDA）受体拮抗剂、一氧化氮合酶（NOS）抑制剂或L型钙通道阻滞剂在减轻化学性缺血、低血糖或氧化应激诱导的细胞损伤方面无效。氧化应激和低血糖显著增加了探针DCFH2-DA的荧光（约1.2倍），这表明细胞内活性氧的形成。用探针二氢罗丹明123（DHR 123）检测到的自由基生成在氧化应激、化学性缺血或低血糖后增强（约2倍）。然而，抗氧化剂维生素E或艾地苯醌对细胞内活性氧的生成无效。化学性缺血后细胞能量电荷大幅下降，低血糖后受到中度影响，但氧化应激后未观察到显著变化。维生素E预孵育可防止低血糖后6小时能量电荷的变化。我们可以得出结论，化学性缺血期间发生的不可逆变化主要反映了缺血核心区域发生的改变，而低血糖情况可能反映了半暗带区域发生的变化，由此维生素E或艾地苯醌可能有助于提高细胞存活率，发挥有益的神经保护作用。
