Müller U, Krieglstein J
Institut für Pharmakologie und Toxikologie, Philipps-Universität, Marburg, Germany.
J Cereb Blood Flow Metab. 1995 Jul;15(4):624-30. doi: 10.1038/jcbfm.1995.77.
The antioxidant dihydrolipoic acid has been shown to reduce hypoxic and excitotoxic neuronal damage in vitro. In the present study, we tested whether pretreatment with alpha-lipoic acid, which presumably allows endogenous formation of dihydrolipoic acid, can protect cultured neurons against injury caused by cyanide, glutamate, or iron ions, using the trypan blue exclusion method to determine neuronal damage. One hour of preincubation with dihydrolipoic acid (1 microM), but not with alpha-lipoic acid, reduced damage of neurons from chick embryo telencephalon caused by 1 mM sodium cyanide or iron ions. alpha-Lipoic acid (1 microM) reduced cyanide-induced neuronal damage when added 24 h before hypoxia, and pretreatment with alpha-lipoic acid for > 24 h enhanced this neuroprotective effect. Both the R- and the S-enantiomer of alpha-lipoic acid exerted a similar neuroprotective effect. Pretreatment with alpha-lipoic acid (1 microM) from the day of plating onward prevented the degeneration of chick embryo telencephalic neurons that had been exposed to Fe2+/Fe3+. alpha-Lipoic acid (1 microM) added to the culture medium the day of plating also reduced neuronal injury induced by 1 mM L-glutamate in rat hippocampal cultures, whereas 30 min of preincubation with alpha-lipoic acid failed to attenuate glutamate-induced neuronal damage. Our results indicate that neuroprotection by prolonged pretreatment with alpha-lipoic acid is probably due to the radical scavenger properties of endogenously formed dihydrolipoic acid.
抗氧化剂二氢硫辛酸已被证明在体外可减少缺氧和兴奋性毒性所致的神经元损伤。在本研究中，我们使用台盼蓝排斥法测定神经元损伤，以测试用α-硫辛酸预处理（据推测可使内源性生成二氢硫辛酸）是否能保护培养的神经元免受氰化物、谷氨酸或铁离子所致的损伤。用二氢硫辛酸（1微摩尔）预孵育1小时可减少1毫摩尔氰化钠或铁离子对鸡胚端脑神经元的损伤，但用α-硫辛酸预孵育则无此作用。在缺氧前24小时添加α-硫辛酸（1微摩尔）可减少氰化物诱导的神经元损伤，用α-硫辛酸预处理超过24小时可增强这种神经保护作用。α-硫辛酸的R-和S-对映体均发挥类似的神经保护作用。从接种当天起用α-硫辛酸（1微摩尔）预处理可防止暴露于Fe2+/Fe3+的鸡胚端脑神经元变性。在接种当天向培养基中添加α-硫辛酸（1微摩尔）也可减少大鼠海马培养物中1毫摩尔L-谷氨酸诱导的神经元损伤，而用α-硫辛酸预孵育30分钟未能减轻谷氨酸诱导的神经元损伤。我们的结果表明，长期用α-硫辛酸预处理产生的神经保护作用可能归因于内源性生成的二氢硫辛酸的自由基清除特性。
