Toxicological interactions between the mycotoxins deoxynivalenol, nivalenol and their acetylated derivatives in intestinal epithelial cells
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In case of mycotoxin contaminations, food and feedstuff are usually contaminated by more than one toxin. However toxicological data concerning the effects of mycotoxin combinations are sparse. The intestinal epithelium is the first barrier against food contaminants and this constantly renewing organ is particularly sensitive to mycotoxins. The aim of this study was to investigate the effects of deoxynivalenol (DON) and four other type B trichothecenes (TCTB), 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), nivalenol (NIV) and fusarenon-X (FX) alone or in combination on intestinal epithelial cells. Proliferating, non-transformed IPEC-1 cells were exposed to increasing doses of TCTB, alone or in binary mixtures and mycotoxin-induced cytotoxicity was measured with MTT test. The toxicological interactions were assessed using the isobologram-Combination index method. The five tested mycotoxins and their mixtures had a dose-dependent effect on the proliferating enterocytes. DON–NIV, DON–15-ADON and 15-ADON–3-ADON combinations were synergistic, with magnitude of synergy for 10 % cytotoxicity ranging from 2 to 7. The association between DON and 3-ADON also demonstrated a synergy but only at high doses, at lower doses antagonism was noted. Additivity was observed between NIV and FX, and antagonism between DON and FX. These results indicate that the simultaneous presence of mycotoxins in food commodities and diet may be more toxic than predicted from the mycotoxins alone. This synergy should be taken into account considering the frequent co-occurrence of TCTB in the diet.
KeywordsCombination index Cytotoxicity Non-transformed intestinal cell Mycotoxin Synergy Trichothecenes
Median effect dose
Dose reduction index
Inhibitory concentration 50 %
3,(4,5-Dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide
The authors are grateful to Pr. T.C. Chou, Memorial Sloan-Kettering Cancer Center, New York City for kind help in data analysis, and Pr F. A. Abiola, Institut des Sciences Biomédicales Appliquées, Cotonou (Republic of Benin) for fruitful discussion. The authors thank Dr. Woodley for language editing. This work was supported by the ANR-CESA project DON & Co. I.A.K. was supported by a doctoral fellowship from the Government of the Republic of Benin.
Conflict of interest
Authors declare no conflict of interest.
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