Zingales Veronica, Piunti Caterina, Micheli Sara, Cimetta Elisa, Ruiz María-José
Research Group in Alternative Methods for Determining Toxics Effects and Risk Assessment of Contaminants and Mixtures (RiskTox), 46100 Valencia, Spain.
Laboratory of Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Valencia, Spain.
Foods. 2024 Dec 23;13(24):4167. doi: 10.3390/foods13244167.
Mycotoxins are among the most concerning natural toxic food contaminants. Over the years, significant efforts have been made to characterize the risk associated with their exposure. However, assessing their toxicity has so far been elusive due to the lack of adequate models that closely mimic the physiological conditions of human cells . Here, we present the SpheroFlow Device (SFD), an efficient microfluidic platform designed, manufactured, and validated to evaluate mycotoxin-induced cytotoxicity under dynamic and continuous exposure in 3D culture settings. In the present study, we integrated human neuroblastoma SH-SY5Y spheroids into the SFD to assess the acute toxicity induced by the mycotoxins ochratoxin A (OTA) and patulin (PAT). The developed system enabled qualitative and quantitative measurements of concentration-response relationships and provided accurate control over the culture microenvironment. Our findings show that by enhancing 3D culture model by applying dynamic flow, SH-SY5Y spheroids exhibited different sensitivities to OTA and PAT compared to conventional static SH-SY5Y spheroids, confirming the critical role of culture models in mycotoxin toxicity assessment. This is the first study assessing the neurotoxicity of OTA and PAT on 3D neuroblastoma spheroids considering the contribution of fluid flow.
霉菌毒素是最令人担忧的天然有毒食品污染物之一。多年来，人们为描述与接触霉菌毒素相关的风险付出了巨大努力。然而，由于缺乏能紧密模拟人类细胞生理条件的适当模型，迄今为止评估它们的毒性一直难以实现。在此，我们展示了SpheroFlow装置（SFD），这是一个经过设计、制造和验证的高效微流控平台，用于在3D培养环境中动态连续暴露下评估霉菌毒素诱导的细胞毒性。在本研究中，我们将人神经母细胞瘤SH-SY5Y球体整合到SFD中，以评估霉菌毒素赭曲霉毒素A（OTA）和展青霉素（PAT）诱导的急性毒性。所开发的系统能够对浓度-反应关系进行定性和定量测量，并能对培养微环境进行精确控制。我们的研究结果表明，通过应用动态流动增强3D培养模型，与传统静态SH-SY5Y球体相比，SH-SY5Y球体对OTA和PAT表现出不同的敏感性，证实了培养模型在霉菌毒素毒性评估中的关键作用。这是第一项考虑流体流动的贡献评估OTA和PAT对3D神经母细胞瘤球体神经毒性的研究。
