PDF(Pubmed)
Abstract：
The Fusarium fungi is found in cereals and feedstuffs and may produce mycotoxins, which are secondary metabolites, such as the T-2 toxin (T-2). In this work, we explored the hepatotoxicity of T-2 using microfluidic 3D hepatic cultures. The objectives were: (i) exploring the benefits of microfluidic 3D cultures compared to conventional 3D cultures available commercially (Aggrewell plates), (ii) establishing 3D co-cultures of hepatic cells (HepG2) and stellate cells (LX2) and assessing T-2 exposure in this model, (iii) characterizing the induction of metabolizing enzymes, and (iv) evaluating inflammatory markers upon T-2 exposure in microfluidic hepatic cultures. Our results demonstrated that, in comparison to commercial (large-volume) 3D cultures, spheroids formed faster and were more functional in microfluidic devices. The viability and hepatic function decreased with increasing T-2 concentrations in both monoculture and co-cultures. The RT-PCR analysis revealed that exposure to T-2 upregulates the expression of multiple Phase I and Phase II hepatic enzymes. In addition, several pro- and anti-inflammatory proteins were increased in co-cultures after exposure to T-2.
摘要：
镰刀菌在谷物和饲料中发现，并可能产生霉菌毒素，是次生代谢产物，例如T-2毒素(T-2)。在这项工作中,我们使用微流控3D肝培养探索T-2的肝毒性。目标是：（i）探索与市售常规3D培养物（Aggrewell平板）相比，微流体3D培养物的益处，（ii）建立肝细胞（HepG2）和星状细胞（LX2）的3D共培养，并评估该模型中的T-2暴露，(iii)表征代谢酶的诱导，和(iv)评估微流控肝培养物中T-2暴露后的炎症标志物。我们的研究结果表明,与商业（大容量）3D文化相比，球状体形成得更快，在微流体装置中功能更强。在单培养和共培养中，活力和肝功能随T-2浓度的增加而降低。RT-PCR分析显示，暴露于T-2会上调多种I期和II期肝酶的表达。此外,暴露于T-2后,共培养物中几种促炎和抗炎蛋白增加.
