Abstract
Deoxynivalenol (DON), nivalenol (NIV), T-2 toxin (T2), fumonisin B1 (FB1), zearalenone (ZEA), and moniliformin (MON) mycotoxins are common food and feed contaminants produced by Fusarium spp. However, while they are usually found to co-occur in a large range of commodities, only few data are available on mycotoxin co-exposure effects and cellular response mechanisms. In this study, the individual and combined toxic effects of these fusariotoxins were evaluated on the THP-1 human immune cell line as major fusariotoxins are mostly potent immunomodulators. In particular, four relevant fusariotoxin mixtures, namely DON-MON, DON-FB1, DON-ZEA, and NIV-T2, were studied using several parameters including cell viability as well as the expression of cell surface markers and the main mitogen-activated protein kinases (MAPKs). After 48 h exposure, a reduction of cell viability in a dose-dependent manner was observed for T2, the most cytotoxic mycotoxin, followed by NIV, DON, MON, FB1, and ZEA. Regarding mycotoxin mixtures, they mainly showed antagonism on cell viability reduction. Interestingly, at concentrations inhibiting 50% of cell viability, most viable cells exhibited surface marker loss and thus became potentially non-functional. In addition, during the first 18 h of exposure, the effects of mycotoxin mixtures on early cell apoptosis and necrosis were found to be different from those induced by the toxins alone. At the molecular level, after 1 h exposure of individual and combined mycotoxins, the three main MAPK signaling pathways (p38, SAPK/JNK, and ERK1/2) were activated, highlighting a fast reaction of the exposed cells even at low cytotoxicity levels.
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Abbreviations
- BEA:
-
Beauvericin
- DiOC6(3):
-
3,3′-Dihexyloxacarbocyanine iodide
- DON:
-
Deoxynivalenol
- ENNs:
-
Enniatins
- FB1:
-
Fumonisin B1
- IC50 :
-
Inhibitory concentration 50%
- MAPKs:
-
Mitogen-activated protein kinases
- MON:
-
Moniliformin
- MTP:
-
Mitochondrial transmembrane potential
- MTS:
-
3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
- NIV:
-
Nivalenol
- PS:
-
Phosphatidylserine
- T2:
-
T-2 toxin
- TCT:
-
Trichothecenes
- ZEA:
-
Zearalenone
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Acknowledgements
M-C Smith was funded by the Région Bretagne in the framework of the ARED Mumycel project. The authors are thankful to Arthur Marie (Université de Brest) for his technical assistance with western blot analyses.
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Smith, MC., Madec, S., Troadec, S. et al. Effects of fusariotoxin co-exposure on THP-1 human immune cells. Cell Biol Toxicol 34, 191–205 (2018). https://doi.org/10.1007/s10565-017-9408-7
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DOI: https://doi.org/10.1007/s10565-017-9408-7