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Influence of T-2 and HT-2 Toxin on the Blood-Brain Barrier In Vitro: New Experimental Hints for Neurotoxic Effects

机译:T-2和HT-2毒素对体外血脑屏障的影响:神经毒性作用的新实验提示

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摘要

The trichothecene mycotoxin T-2 toxin is a common contaminant of food and feed and is also present in processed cereal derived products. Cytotoxic effects of T-2 toxin and its main metabolite HT-2 toxin are already well described with apoptosis being a major mechanism of action. However, effects on the central nervous system were until now only reported rarely. In this study we investigated the effects of T-2 and HT-2 toxin on the blood-brain barrier (BBB) in vitro. Besides strong cytotoxic effects on the BBB as determined by the CCK-8 assay, impairment of the barrier function starting at low nanomolar concentrations were observed for T-2 toxin. HT-2 toxin, however, caused barrier disruption at higher concentrations compared to T-2 toxin. Further, the influence on the tight junction protein occludin was studied and permeability of both toxins across the BBB was detected when applied from the apical (blood) or the basolateral (brain) side respectively. These results clearly indicate the ability of both toxins to enter the brain via the BBB.
机译:天花粉真菌毒素T-2毒素是食物和饲料的常见污染物,也存在于谷物加工产品中。 T-2毒素及其主要代谢产物HT-2毒素的细胞毒性作用已得到很好的描述,凋亡是其主要作用机制。然而,迄今为止,对中枢神经系统的影响鲜有报道。在这项研究中,我们研究了T-2和HT-2毒素对体外血脑屏障(BBB)的影响。除了通过CCK-8分析确定对BBB具有强大的细胞毒性作用外,对于T-2毒素,还观察到从低纳摩尔浓度开始的屏障功能受损。但是,与T-2毒素相比,HT-2毒素在较高浓度下会导致屏障破坏。此外,研究了对紧密连接蛋白闭合蛋白的影响,并分别从顶端(血液)或基底外侧(大脑)侧应用两种毒素穿过BBB的通透性。这些结果清楚地表明了两种毒素通过血脑屏障进入大脑的能力。

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