Toxicological interactions between the mycotoxins deoxynivalenol, nivalenol and their acetylated derivatives in intestinal epithelial cells

Abstract

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.

Cytotoxic effects and degradation products of three mycotoxins: Alternariol, 3-acetyl-deoxynivalenol and 15-acetyl-deoxynivalenol in liver hepatocellular carcinoma cells

“…The MTT test, linked to mitochondrial, was used for the indirect measurement of proliferation and viability of HepG2 cells. With this test it was demonstrated that type B trichothecenes, were cytotoxic for HepG2 cells in a dose-dependent manner as previously demonstrated in intestinal cells (Alassane-Kpembi et al, 2014).…”

“…The cytotoxicity of AOH has been widely studied using different cell cultures and assays (Fernández-Blanco et al, 2014;Chiesi et al, 2015;Vila-Donat et al, 2015;Bensassi et al, 2012). Until now, data about cytotoxic effects of 3-ADON and 15-ADON applied individually and in combination is reported in literature in non-transformed intestinal epithelial cell line of a newborn unsuckled piglet (IPEC-1 cells) (Alassane-Kpembi et al, 2014;Pinton et al, 2012), in derived human colon adenocarcinoma cell line (Caco-2 cells) (Alassane- Kpembi et al, 2013); in bovine peripheral blood mononuclear cells (PBMC) (Daenicke et al, 2011), in Swiss mouse 3T3 fibroblasts (Sundstol et al, 2004. However, the number of European in vitro studies in the last 15 years reporting 3-ADON or 15-ADON treatment on HepG2 cell lines is scarce.…”

Modeling the emetic potencies of food-borne trichothecenes by benchmark dose methodology

“…Another limitation to the TEF approach for trichothecenes is that very few studies have evaluated their potential interactions and consequent effects in animals and yet we know that these toxins typically co-occur in food (Bertuzzi et al, 2014; Desjardins et al, 2007; Ibáñez-Vea et al, 2012; Pronk et al, 2002; Šegvić Klarić, 2012). Although a recent investigation reported some synergistic toxic effects in vitro (Alassane-Kpembi et al, 2014), these are inconclusive since there is still uncertainty over the nature of interactions in vivo . Therefore, more research on emetic responses induced by mixtures of these mycotoxins using animal models is needed to inform risk assessment.…”

Occurrence of Fusarium Mycotoxins in Cereal Crops and Processed Products (Ogi) from Nigeria

“…Harvey et al [13] and Kubena et al [14] demonstrated the synergistic and additive effects resulting to growth depression in pigs and broiler chicks, respectively because of co-occurrence of mixed mycotoxins (DON and FB 1 ). A synergistic interaction between several combinations of type B TH on epithelial cell toxicity has also been recorded [11,15]. Recently, issues of possible co-existence of these Fusarium mycotoxins and their modified forms have become of great concern.…”