National Reference Laboratory of Veterinary Drug Residues (HZAU)/Key Laboratory for the Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
Toxicol Sci. 2014 Jan;137(1):168-78. doi: 10.1093/toxsci/kft233. Epub 2013 Oct 17.
Though T-2 toxin is the most harmful mycotoxin to the fetuses, it remains unclear whether T-2 toxin and its major metabolite, HT-2 toxin, could pass the placenta into the fetus and which kind of placental transport is involved in the passage. To illustrate their placenta transfer mechanism, the uptake and efflux of T-2 and HT-2 toxins across apical membranes of placenta with BeWo cells as a model were studied at different temperatures, pHs, and in the presence of transporter inhibitors with a developed liquid chromatography-tandem mass spectrometry to determine the amount of toxins in both fetal and maternal sites. Higher unidirectional transport of T-2 toxin was observed in the apical-to-basolateral direction than basolateral-to-apical one, whereas HT-2 toxin exhibited similar transport rate from the 2 directions. The main ATP-binding cassette transporters had no effect on the efflux of 2 toxins. Initial uptake of T-2 toxin was sodium dependent and saturable, and the apical uptake was temperature dependent and enhanced under acidic condition. The apical uptake of T-2 toxin was inhibited by metabolic inhibitors and the organic anion and organic cation transporter inhibitors. These results suggested that an active transport mechanism was responsible for the uptake of T-2 toxin, whereas passive diffusion was the principal mechanism for HT-2 toxin transport in the placenta. Taken together, these data characterized the placental transfer of T-2 and HT-2 toxins. The present study offered new ways of reducing the risks of T-2 and HT-2 toxins to both mother and fetuses.
虽然 T-2 毒素是对胎儿最有害的真菌毒素，但 T-2 毒素及其主要代谢物 HT-2 毒素是否能通过胎盘进入胎儿体内，以及哪种胎盘转运方式参与了这种转移，目前仍不清楚。为了阐明它们的胎盘转运机制，我们以 BeWo 细胞为模型，研究了 T-2 和 HT-2 毒素在不同温度、pH 值以及转运体抑制剂存在下穿过胎盘顶膜的摄取和外排情况，并用开发的液相色谱-串联质谱法来测定胎儿和母体部位毒素的含量。结果显示，T-2 毒素在顶侧到基底侧的单向转运高于基底侧到顶侧，而 HT-2 毒素在这两个方向的转运率相似。主要的 ATP 结合盒转运体对 2 种毒素的外排没有影响。T-2 毒素的初始摄取依赖于钠离子且是饱和的，顶侧摄取依赖于温度且在酸性条件下增强。T-2 毒素的顶侧摄取被代谢抑制剂和有机阴离子及有机阳离子转运体抑制剂所抑制。这些结果表明，主动转运机制负责 T-2 毒素的摄取，而 HT-2 毒素在胎盘内的转运主要是通过被动扩散。综上所述，这些数据描述了 T-2 和 HT-2 毒素的胎盘转运。本研究为降低 T-2 和 HT-2 毒素对母亲和胎儿的风险提供了新的途径。
