Willis C L, Meldrum B S, Nunn P B, Anderton B H, Leigh P N
Department of Neurology, Institute of Psychiatry, London, UK.
Neurosci Lett. 1994 Dec 5;182(2):159-62. doi: 10.1016/0304-3940(94)90787-0.
The neurotoxin beta-N-oxalylamino-L-alanine (BOAA), found in Lathyrus sativus seeds, is thought to be the causative agent of neurolathyrism. We have investigated the neuroprotective effects of free radical scavengers on BOAA-induced toxicity following focal injection (1 microliter) of BOAA and comparing the pathological outcome with the effects of injections of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA), kainate (KA) or N-methyl-D-aspartate (NMDA) into the dorsal hippocampus of male Wistar rats. Cellular damage was assessed histologically. BOAA (50 nmol) induced a highly selective pattern of hippocampal damage identical with that seen with AMPA (1 nmol). BOAA-induced neurotoxicity, but not AMPA, KA (0.5 nmol) or NMDA (25 nmol)-induced neurotoxicity, was prevented in a dose-dependent manner by focal co-injection of four potential free radical scavengers; dimethyl sulphoxide (DMSO) (1750-7000 nmol), dimethylthiourea (DMTU) (8000 nmol), dimethylformamide (DMF) (7000 nmol) and mannitol (1000 nmol). These findings suggest that hippocampal damage induced by BOAA involves an interaction between AMPA receptors and free radicals.
在山黧豆种子中发现的神经毒素β-N-草酰基-L-丙氨酸（BOAA）被认为是神经性山黧豆中毒的病原体。我们研究了自由基清除剂对在雄性Wistar大鼠背侧海马局部注射（1微升）BOAA后其诱导的毒性的神经保护作用，并将病理结果与向其中注射α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）、红藻氨酸（KA）或N-甲基-D-天冬氨酸（NMDA）的效果进行比较。通过组织学评估细胞损伤情况。BOAA（50纳摩尔）诱导出一种高度选择性的海马损伤模式，与AMPA（1纳摩尔）诱导的损伤模式相同。通过局部共同注射四种潜在的自由基清除剂；二甲基亚砜（DMSO）（1750 - 7000纳摩尔）、二甲基硫脲（DMTU）（8000纳摩尔）、二甲基甲酰胺（DMF）（7000纳摩尔）和甘露醇（1000纳摩尔），BOAA诱导的神经毒性以剂量依赖性方式得到预防，但AMPA、KA（0.5纳摩尔）或NMDA（25纳摩尔）诱导的神经毒性未得到预防。这些发现表明，BOAA诱导的海马损伤涉及AMPA受体与自由基之间的相互作用。
