Institute of Food Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstrasse 45, Münster, Germany.
Chem Res Toxicol. 2013 Mar 18;26(3):347-55. doi: 10.1021/tx3004664. Epub 2013 Feb 14.
The trichothecene mycotoxin T-2 toxin, which is produced by fungi of the Fusarium species, is a worldwide occurring contaminant of cereal based food and feed. The cytotoxic properties of T-2 toxin are already well described with apoptosis being a major mechanism of action in various cell lines as well as in primary cells of different origin. However, only few data on neurotoxic properties of T-2 toxin are reported so far, but in vivo studies showed different effects of T-2 toxin on behavior as well as on levels of brain amines in animals. To further investigate the cytotoxic properties of T-2 toxin on cells derived from brain tissue, normal human astrocytes in primary culture (NHA) were used in this study. Besides studies of cytotoxicity, apoptosis (caspase-3-activation, Annexin V) and necrosis (LDH-release), the cellular uptake and metabolism of T-2 toxin in NHA was analyzed and compared to the uptake in an established human cell line (HT-29). The results show that human astrocytes were highly sensitive to the cytotoxic properties of T-2 toxin, and apoptosis, induced at low concentrations, was identified for the first time as the mechanism of toxic action in NHA. Furthermore, a strong accumulation of T-2 toxin in NHA and HT-29 cells was detected, and T-2 toxin was subjected to metabolism leading to HT-2 toxin, a commonly found metabolite after T-2 toxin incubation in both cell types. This formation seems to occur within the cells since incubations of T-2 toxin with cell depleted culture medium did not lead to any degradation of the parent toxin. The results of this study emphasize the neurotoxic potential of T-2 toxin in human astrocytes at low concentrations after short incubation times.
三脱氧镰刀菌烯醇（T-2 毒素）是一种由镰刀菌属真菌产生的霉菌毒素，是世界范围内谷物类食品和饲料的污染物。T-2 毒素的细胞毒性特性已经得到了很好的描述，凋亡是其在各种细胞系以及不同来源的原代细胞中的主要作用机制。然而，目前关于 T-2 毒素的神经毒性特性的报道很少，但体内研究表明，T-2 毒素对动物行为和大脑胺水平有不同的影响。为了进一步研究 T-2 毒素对脑组织来源细胞的细胞毒性特性，本研究使用原代培养的正常人星形胶质细胞（NHA）。除了细胞毒性研究外，还分析和比较了 T-2 毒素在 NHA 中的摄取和代谢，并与已建立的人细胞系（HT-29）中的摄取进行比较。结果表明，人星形胶质细胞对 T-2 毒素的细胞毒性非常敏感，并且首次在 NHA 中鉴定出低浓度诱导的凋亡是其毒性作用的机制。此外，在 NHA 和 HT-29 细胞中检测到 T-2 毒素的强烈积累，并发现 T-2 毒素发生代谢，生成 HT-2 毒素，这是在这两种细胞类型中孵育 T-2 毒素后常见的代谢产物。由于与细胞耗尽的培养基孵育的 T-2 毒素不会导致母体毒素降解，因此该形成似乎发生在细胞内。本研究的结果强调了 T-2 毒素在短孵育时间后对人星形胶质细胞的低浓度的神经毒性潜力。
