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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。

Influence of T-2 and HT-2 toxin on the blood-brain barrier in vitro: new experimental hints for neurotoxic effects.

机构信息

Institute of Food Chemistry, Westfälische Wilhelms-Universität Münster, Münster, Germany.

出版信息

PLoS One. 2013;8(3):e60484. doi: 10.1371/journal.pone.0060484. Epub 2013 Mar 27.

Abstract

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.

摘要

T-2 毒素是一种常见的真菌毒素,存在于食物和饲料中,也存在于加工谷物衍生产品中。T-2 毒素及其主要代谢物 HT-2 毒素的细胞毒性作用已经得到了很好的描述,细胞凋亡是其主要作用机制。然而,到目前为止,关于其对中枢神经系统的影响的报道还很少。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 CCK-8 测定法确定的对 BBB 的强烈细胞毒性作用外,还观察到 T-2 毒素在低纳摩尔浓度下就会损害屏障功能。相比之下,HT-2 毒素在更高的浓度下才会引起屏障破坏。此外,还研究了紧密连接蛋白紧密连接蛋白 occludin 的影响,并检测了两种毒素分别从顶端(血液)或基底外侧(脑)侧应用时穿过 BBB 的通透性。这些结果清楚地表明了这两种毒素都有穿过血脑屏障进入大脑的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d754/3609806/24e8ebe53402/pone.0060484.g001.jpg

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