Antonio Angeline M, Druse Mary J
Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Stritch School of Medicine, Maywood, IL 60153, USA.
Brain Res. 2008 Apr 14;1204:16-23. doi: 10.1016/j.brainres.2008.02.018. Epub 2008 Feb 19.
It is well known that ethanol damages the developing nervous system by augmenting apoptosis. Previously, this laboratory reported that ethanol augments apoptosis in fetal rhombencephalic neurons, and that the increased apoptosis is associated with reduced activity of the phosphatidylinositol 3-kinase pathway and downstream expression of pro-survival genes. Other laboratories have shown that another mechanism by which ethanol induces apoptosis in developing neurons is through the generation of reactive oxygen species (ROS) and the associated oxidative stress. The present study used an in vitro model to investigate the potential neuroprotective effects of several antioxidants against ethanol-associated apoptosis in fetal rhombencephalic neurons. The investigated antioxidants included three phenolics: (-)-epigallocatechin-3-gallate (EGCG), a flavanoid polyphenol found in green tea; curcumin, found in tumeric; and resveratrol (3,5,4'-trihydroxystilbene), a component of red wine. Additional antioxidants, including melatonin, a naturally occurring indole, and alpha-lipoic acid, a naturally occurring dithiol, were also investigated. These studies demonstrated that a 24-hour treatment of fetal rhombencephalic neurons with 75 mM ethanol caused a 3-fold increase in the percentage of apoptotic neurons. However, co-treatment of these cultures with any of the five different antioxidants prevented ethanol-associated apoptosis. Antioxidant treatment did not alter the extent of apoptosis in control neurons, i.e., those cultured in the absence of ethanol. These studies showed that several classes of antioxidants can exert neuroprotection against ethanol-associated apoptosis in fetal rhombencephalic neurons.
众所周知，乙醇通过增加细胞凋亡来损害发育中的神经系统。此前，本实验室报告称，乙醇会增加胎儿菱脑神经元的细胞凋亡，且细胞凋亡增加与磷脂酰肌醇3-激酶途径活性降低及促生存基因的下游表达有关。其他实验室表明，乙醇在发育中的神经元中诱导细胞凋亡的另一种机制是通过产生活性氧（ROS）及相关的氧化应激。本研究使用体外模型来研究几种抗氧化剂对胎儿菱脑神经元中乙醇相关细胞凋亡的潜在神经保护作用。所研究的抗氧化剂包括三种酚类物质：（-）-表没食子儿茶素-3-没食子酸酯（EGCG），一种存在于绿茶中的类黄酮多酚；姜黄素，存在于姜黄中；以及白藜芦醇（3,5,4'-三羟基芪），红酒的一种成分。还研究了其他抗氧化剂，包括天然存在的吲哚褪黑素和天然存在的二硫醇α-硫辛酸。这些研究表明，用75 mM乙醇对胎儿菱脑神经元进行24小时处理会使凋亡神经元的百分比增加3倍。然而，用这五种不同抗氧化剂中的任何一种对这些培养物进行共同处理可防止乙醇相关的细胞凋亡。抗氧化剂处理并未改变对照神经元（即在无乙醇条件下培养的神经元）中的细胞凋亡程度。这些研究表明，几类抗氧化剂可对胎儿菱脑神经元中乙醇相关的细胞凋亡发挥神经保护作用。
