The emerging mycotoxin, enniatin B1, down-modulates the gastrointestinal toxicity of T-2 toxin in vitro on intestinal epithelial cells and ex vivo on intestinal explants

Abstract

Enniatins, the most prevalent emerging mycotoxins, represent an emerging food safety issue, because of their common co-occurrence with other fusariotoxins such as trichothecenes co-produced by Fusarium spp on field grains and because of their extensive prevalence in grains. In this study, the intestinal toxicity of enniatin B1 (ENN) alone and mixed with the most toxic trichothecene T-2 toxin (T2) was characterized by using two biological models from pig, the most sensitive species: the intestinal cell line IPEC1 (in vitro exposure) and jejunal explants (ex vivo exposure). Dose-dependent decreases in cell proliferation in IPEC1 and in the histopathological scores of explants were observed for ENN at μM-levels and for T2 at nM-levels, with IC50 values for ENN of 15.8 and 29.7 μM, and for T2 of 9.3 and 15.1 nM in vitro and ex vivo, respectively. Interaction analysis by probabilistic and by determinist approaches showed a less than additive effect both in vitro and ex vivo, at IC50 values, with increasing antagonism with decreasing concentrations of toxins. The results obtained by the determinist median-effect dose analysis and by the nonlinear regression analysis were concordant. All the median-effect doses estimated for IPEC cells were included in the IC50 confidence intervals of the nonlinear regression fitting. Given the occurrence of enniatins, potential synergy following the co-occurrence of enniatins and the major fusariotoxins, especially trichothecene B deoxynivalenol should be investigated.

Recent aflatoxin survey data in milk and milk products: A review

“…These are secondary fungal metabolites with various chemical structures and properties, which create a variety of toxic effects in humans and animals. These toxic effects include acute toxicity (De Melo et al 2012;Kolf-Clauw et al 2013), carcinogenicity (Marin-Kuan et al 2011;Zain 2011;Ferrante et al 2012;Marin et al 2013), mutagenicity (Fleck et al 2012;Domijan et al 2014) and teratogenicity (Lather et al 2011), which occur in animals and humans at different levels of contamination.…”

Nivalenol Has a Greater Impact than Deoxynivalenol on Pig Jejunum Mucosa in Vitro on Explants and in Vivo on Intestinal Loops

“…Two alternative models were used in this study to analyze intestinal mucosal toxicity, a major target for xenobiotics. An explant model, previously shown to be sensitive [ 23 , 24 ], was first used to demonstrate dose-related toxicity following in vitro exposure to DON and NIV, and a higher toxicity of NIV. This result was then confirmed in vivo , using the intestinal loops model.…”

“…The procedure for the culture of explants was as previously described [ 23 , 24 ]. Explants were incubated for 4 h with WME at 37 °C under a CO 2 -controlled atmosphere with orbital shaking.…”

“…The culture of intestinal explants allows preservation of the normal histological structure in vitro [ 20 ]. The pig jejunal explant model has previously been used to study the digestive effects of the mycotoxin DON [ 21 , 22 , 23 ], and to analyze the toxicity of mixtures of mycotoxins [ 24 ]. The present work was designed to compare the acute impacts of DON and NIV on pig jejunal mucosa.…”

Enniatin-containing solutions for oromucosal use: Quality-by-design ex-vivo transmucosal risk assessment of composition variability

“…Therefore, the overall objective of this study was to quantitatively evaluate the transmucosal kinetics of enniatins, using excised porcine buccal mucosa in an ex-vivo in-vitro FDC set-up with the application of a quality-by-design (QbD) risk assessment of the quantitative excipient composition variability. This is of pivotal importance, since enniatins have recently been identified as mycotoxins, which are secondary metabolites produced by fungi, posing a health hazard by exerting a toxic activity on human or animal cells (Jestoi, 2008;Tedjiotsop Feudjio et al, 2010;Faeste et al, 2011;Kolf-Clauw et al, 2013;Devreese et al, 2014;Taevernier et al, 2015). The European Food and Safety Authority (EFSA) recently published their "scientific opinion on the risks to human and animal health related to the presence of beauvericin and enniatins in food and feed".…”