Boland A, Delapierre D, Mossay D, Hans P, Dresse A
Laboratory of Pharmacology, Institute of Pathology B23, University of Liege, B-4000, Liege, Belgium.
Eur J Pharmacol. 2000 Sep 15;404(1-2):21-7. doi: 10.1016/s0014-2999(00)00496-9.
The anesthetic propofol (PPF) has been shown to be an antioxidant in acellular experiments. This study was designed to assess the ability of PPF to protect primary-cultured brain cells against iron-mediated toxicity. A comparison with trolox (TX), a hydrosoluble vitamin E analogue, was performed. Rat cortical cells were exposed to 10 microM FeSO(4), PPF and/or TX. After a 4-h incubation, PPF and TX improved cell survival (lactate dehydrogenase measurements) in a concentration-dependent manner. The respective EC(50s) of each substance were 4 and 4.6 microM. The maximal effect was obtained at a 25-microM concentration which is similar to concentrations of PPF used clinically. The combination of both drugs at certain concentrations showed a complete protection of the cells, a significant decrease in intracellular peroxide production (dichloro-fluorescein diacetate (DCF-DA) fluorescence, 4-h incubation), in lipoperoxidation (thiobarbituric acid reactive substances fluorescence, PPF 6.25 microM+TX 12.5 microM) and an additive protective effect. This was true after 4- and 16-h incubation. These data suggest that PPF is neuroprotective. Moreover, the combination with a vitamin E analogue confers long duration protection against oxidative stress.
麻醉剂丙泊酚（PPF）在无细胞实验中已被证明是一种抗氧化剂。本研究旨在评估PPF保护原代培养的脑细胞免受铁介导毒性的能力。同时与水溶性维生素E类似物托可索仑（TX）进行了比较。将大鼠皮质细胞暴露于10微摩尔硫酸亚铁、PPF和/或TX中。孵育4小时后，PPF和TX以浓度依赖性方式提高了细胞存活率（通过乳酸脱氢酶测量）。每种物质的半数有效浓度（EC50）分别为4微摩尔和4.6微摩尔。在25微摩尔浓度时可获得最大效应，这与临床使用的PPF浓度相似。两种药物在特定浓度下联合使用可完全保护细胞，显著降低细胞内过氧化物生成（二氯荧光素二乙酸酯（DCF-DA）荧光，孵育4小时）、脂质过氧化（硫代巴比妥酸反应性物质荧光，PPF 6.25微摩尔+TX 12.5微摩尔），并具有相加的保护作用。在孵育4小时和16小时后均如此。这些数据表明PPF具有神经保护作用。此外，与维生素E类似物联合使用可提供针对氧化应激的长期保护。
