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Cytotoxic effects of mycotoxin combinations in mammalian kidney cells
María-José Ruiz1, Petra Macáková, Ana Juan-García
1Laboratori de Toxicologia, Facultat de Farmacia, Universitat de Valencia, Av. Vicent Andres Estelles, 46100 Burjassot, Valencia, Spain. M.Jose.Ruiz@uv.es
Abstract:
The cytotoxicity of three Fusarium mycotoxins (beauvericin, deoxynivalenol and T-2 toxin) has been investigated using the NR assay, after 24, 48 and 72h of incubation. The IC(50) values ranged from 6.77 to 11.08, 3.30 to 10.00 and 0.004 to 0.005 for beauvericin, deoxynivalenol and T-2 toxin, respectively. Once the potential interaction has been detected, a quantitative assessment is necessary to ensure and characterize these interactions, that is, each mycotoxin contributes to the toxic effect in accord with its own potency. Combination of mycotoxins was determined in Vero cells after 24, 48 and 72h of exposure. Isobolograms and median effect method of Chou and Talalay were used to assess the nature and quantitative aspects of interaction observed between studied mycotoxins. Median effect analysis was used to calculate the combination index (CI) with values >1 indicating synergism, 1 additive effect, and <1 antagonism. CI values of BEA+DON (1.22-2.74), BEA+T-2 toxin (1.43-5.89), DON+T-2 toxin (3.13-7.62) and BEA+DON+T-2 toxin (1.32-2.68) for 24, 48 and 72h produced antagonistic effects in Vero cells. The highest antagonistic effect in Vero cells was observed with binary DON and T-2 toxin mixture.
Insights
This study investigated the cytotoxic effects of beauvericin, deoxynivalenol, and T-2 toxin on Vero cells. Mycotoxin combinations exhibited antagonistic effects, with DON and T-2 toxin showing the strongest interaction.
Area of Science:
- Toxicology
- Mycotoxicology
- Cell Biology
Background:
- Fusarium mycotoxins pose a significant threat to human and animal health.
- Understanding the cytotoxic interactions of these toxins is crucial for risk assessment.
Purpose of the Study:
- To evaluate the cytotoxicity of beauvericin (BEA), deoxynivalenol (DON), and T-2 toxin individually.
- To determine the interaction effects of mycotoxin combinations (BEA+DON, BEA+T-2, DON+T-2, and BEA+DON+T-2) in Vero cells.
Main Methods:
- Cytotoxicity was assessed using the Neutral Red (NR) assay over 24, 48, and 72 hours.
- The Chou and Talalay median effect method and isobolograms were employed to quantify mycotoxin interactions.
- Combination Index (CI) values were calculated to determine synergistic, additive, or antagonistic effects.
Main Results:
- Individual IC(50) values indicated varying cytotoxicity levels for each mycotoxin.
- All tested combinations of beauvericin, deoxynivalenol, and T-2 toxin demonstrated antagonistic effects in Vero cells.
- The DON and T-2 toxin binary mixture exhibited the most pronounced antagonistic interaction.
Conclusions:
- Beauvericin, deoxynivalenol, and T-2 toxin display distinct cytotoxic profiles.
- Mycotoxin combinations do not act additively or synergistically; instead, they exhibit antagonism.
- Further research is needed to elucidate the mechanisms underlying these antagonistic interactions in cellular systems.
