1. Using Microfluidic Hepatic Spheroid Cultures to Assess Liver Toxicity of T-2 Mycotoxin
- Author
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Mercedes Taroncher, Alan M. Gonzalez-Suarez, Kihak Gwon, Samuel Romero, Angel D. Reyes-Figueroa, Yelko Rodríguez-Carrasco, María-José Ruiz, Gulnaz Stybayeva, Alexander Revzin, and Jose M. de Hoyos-Vega
- Subjects
T-2 ,HepG2 cells ,microfluidic devices ,spheroids ,cytotoxicity ,Cytology ,QH573-671 - 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.
- Published
- 2024
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