Taroncher Mercedes, Franco-Campos Felipe, Rodríguez-Carrasco Yelko, Ruiz María-José
Research Group in Alternative Methods for Determining Toxics Effects and Risk Assessment of Contaminants and Mixtures (RiskTox), University of Valencia, 46100 Valencia, Spain.
Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy and Food Sciences, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Valencia, Spain.
Toxins (Basel). 2025 Aug 8;17(8):397. doi: 10.3390/toxins17080397.
The T-2 toxin is one of the most toxic mycotoxins, to which the population is exposed through the diet. T-2 toxins are especially found in cereals and cereal-based products. To deepen our understanding of the mechanisms of T-2 toxin action, the morphological changes, oxidative stress, and inflammatory response of this mycotoxin have been evaluated in HepG2 cells. The mRNA and protein expression levels of inflammatory cytokines such as IL-1β, IL-6, and TNF-α and proteins such as Nrf2 and HO-1 were analyzed after T-2 exposure (7.5, 15, and 30 nM) by qPCR and Western blot assays. Firstly, changes in the morphology of HepG2 cells after T-2 exposure from circular to elongated shape were observed in a concentration-dependent manner by indirect immunofluorescence. These alterations may reflect early signs of cell stress. The results revealed an upregulation of the mRNA of IL-1β, IL-6, and TNF-α after T-2 exposure, with the highest increase in TNF-α after 30 nM T-2, suggesting a proinflammatory effect. Regarding the oxidative response, HO-1 at the lowest T-2 concentration was upregulated. However, the Nrf2 at all T-2 concentrations tested was downregulated. These findings were corroborated by Western blot analysis. These results confirm that T-2 hepatotoxicity produces an increase in key inflammatory cytokines, modulates the Nrf2/HO-1 pathway, and produces morphological changes in HepG2 cells. The next step would be to test whether a co-exposure of natural antioxidants with T-2 exerts a cytoprotective effect.
T-2毒素是毒性最强的霉菌毒素之一，人们通过饮食接触到这种毒素。T-2毒素尤其常见于谷物及谷物制品中。为了更深入地了解T-2毒素的作用机制，研究人员在HepG2细胞中评估了这种霉菌毒素的形态变化、氧化应激和炎症反应。通过qPCR和蛋白质免疫印迹分析，检测了T-2毒素暴露（7.5、15和30 nM）后炎症细胞因子如IL-1β、IL-6和TNF-α的mRNA和蛋白质表达水平，以及Nrf2和HO-1等蛋白质的表达水平。首先，通过间接免疫荧光观察到，T-2毒素暴露后HepG2细胞的形态从圆形变为细长形，且呈浓度依赖性。这些变化可能反映了细胞应激的早期迹象。结果显示，T-2毒素暴露后IL-1β、IL-6和TNF-α的mRNA上调，30 nM T-2毒素作用后TNF-α的增加最为显著，表明其具有促炎作用。关于氧化反应，最低浓度T-2毒素作用下HO-1上调。然而，所有测试浓度的T-2毒素作用下Nrf2均下调。蛋白质免疫印迹分析证实了这些发现。这些结果证实，T-2毒素的肝毒性导致关键炎症细胞因子增加，调节Nrf2/HO-1通路，并使HepG2细胞产生形态变化。下一步将测试天然抗氧化剂与T-2毒素共同暴露是否具有细胞保护作用。
