Low doses of the mycotoxin citrinin protect cortical neurons against glutamate-induced excitotoxicity
Low doses of the mycotoxin citrinin protect cortical neurons against glutamate-induced excitotoxicity
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DOI：
10.2131/jts.41.311
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发表时间：
2016-04-01
影响因子：
2
通讯作者：
Shinoda, Yo
中科院分区：
文献类型：
--
作者：
Nakajima, Yui;Iguchi, Hirotoshi;Shinoda, Yo
柠檬酸钠是一种天然真菌毒素，存在于发酵食品中，被称为细胞毒素和肾毒素。暴露于高剂量的黄嘌呤导致细胞凋亡；然而，低剂量的影响尚不完全清楚。谷氨酸兴奋性毒性是急性神经系统疾病（包括中风、创伤和其他神经退行性疾病）中神经元死亡的原因。在这里，我们展示了低剂量黄嘌呤对谷氨酸诱导的兴奋性毒性的神经保护作用。在两种情况下，我们检测了黄嘌呤暴露对谷氨酸诱导的大鼠皮质神经元细胞死亡的影响：黄嘌呤与谷氨酸（30 μ M）同时处理0.1 ~ 1,000 nM，持续1,3小时；柠檬酸苷预处理21小时后，同样同时处理3小时。MTT和免疫细胞化学试验在几个剂量和暴露时间下都显示出显著的神经保护作用。所有浓度的柑橘霉素暴露14天后均未显示出显著的细胞死亡，突触也没有明显改变。这些数据表明，低剂量的黄嘌呤可以作为抗谷氨酸诱导的兴奋性毒性的神经保护剂，而不会造成额外的有害细胞改变。
Citrinin, a natural mycotoxin that is found in fermented foods, is known as a cytotoxin and nephrotoxin. Exposure to high doses of citrinin result in apoptosis; however, the effects of low doses are not fully understood. Glutamate excitotoxicity is responsible for neuronal death in acute neurological disorders including stroke, trauma and other neurodegenerative diseases. Here, we show the neuroprotective effect of low doses of citrinin against glutamate-induced excitotoxicity. We examined the effect of citrinin exposure on glutamate-induced cell death in cultured rat cortical neurons under two conditions: simultaneous treatment with citrinin 0.1 to 1,000 nM and glutamate (30 mu M) for 1, 3 hr; the same simultaneous treatment for 3 hr after pretreatment with citrinin for 21 hr. Both the MTT and immunocytochemical assay showed significant neuroprotective effects at several doses and exposure times tested. All concentrations of citrinin tested showed no remarkable cell death following 14-day exposure, and no marked alterations to synapses. These data suggest that low doses of citrinin can be used as a neuroprotective agent against glutamate-induced excitotoxicity without additional harmful cellular alterations.