New insights into mycotoxin mixtures: The toxicity of low doses of Type B trichothecenes on intestinal epithelial cells is synergistic

Abstract

Deoxynivalenol (DON) is the most prevalent trichothecene mycotoxin in crops in Europe and North America. DON is often present with other type B trichothecenes such as 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), nivalenol (NIV) and fusarenon-X (FX). Although the cytotoxicity of individual mycotoxins has been widely studied, data on the toxicity of mycotoxin mixtures are limited. The aim of this study was to assess interactions caused by co-exposure to Type B trichothecenes on intestinal epithelial cells. Proliferating Caco-2 cells were exposed to increasing doses of Type B trichothecenes, alone or in binary or ternary mixtures. The MTT test and neutral red uptake, respectively linked to mitochondrial and lysosomal functions, were used to measure intestinal epithelial cytotoxicity. The five tested mycotoxins had a dose-dependent effect on proliferating enterocytes and could be classified in increasing order of toxicity: 3-ADON<15-ADON≈DON<NIV≪FX. Binary or ternary mixtures also showed a dose-dependent effect. At low concentrations (cytotoxic effect between 10 and 30-40%), mycotoxin combinations were synergistic; however DON-NIV-FX mixture showed antagonism. At higher concentrations (cytotoxic effect around 50%), the combinations had an additive or nearly additive effect. These results indicate that the simultaneous presence of low doses of mycotoxins in food commodities and diet may be more toxic than predicted from the mycotoxins alone. Considering the frequent co-occurrence of trichothecenes in the diet and the concentrations of toxins to which consumers are exposed, this synergy should be taken into account.

Evaluation of the proliferative activity of immunocompetent cells in the jejunal and iliac lymph nodes of prepubertal female wild boars diagnosed with mixed mycotoxicosis

“…Similar results were reported by Alassane-Kpembi et al (1) in a study on pigs. Synergistic interactions can occur at different stages in the same toxicity pathway, or when the presence of one mycotoxin increases absorption or decreases the metabolic degradation of another mycotoxin (27,28,6).…”

Patulin, Deoxynivalenol, Zearalenone and T-2 Toxin Affect Viability and Modulate Cytokine Secretion in J774A.1 Murine Macrophages

“…8, No. 2;2016Bianco et al, 2012Alassane-Kpembi et al, 2013;Clarke et al, 2014;Solhaug et al, 2015), but there is a lack of understanding of the exact mechanisms behind the interactions involved. The effects of individual toxins can vary depending on concentration, time and other environmental factors.…”

“…Immunosuppression is viewed as one of the most significant effects of mycotoxin exposure and it has a major economic impact. Studies have already highlighted the immunosuppressive nature of several mycotoxins such as aflatoxins, trichothecenes, ochratoxin A and zearalenone (Ferrante et al, 2002;Sharma et al, 2004;Ferrante et al, 2008;Ubagai et al, 2008;Marzocco et al, 2009;Bianco et al, 2012;Bruneau et al, 2012;Alassane-Kpembi et al, 2013;Jia et al, 2014). Immunostimulation and immunosuppression can occur with the same toxin depending on the exposure conditions, including dosage and time.…”

Differences in the Toxicities of Trichothecene Mycotoxins, Deoxynivalenol and Nivalenol, in Cultured Cells

“…investigated (Alassane-Kpembi et al 2013, Speijers and Speijers 2004, Wan et al 2013. Group tolerable daily intake (TDI) is a superb concept to regulate toxins, because governments need not set regulatory values for each toxin.…”