Toxicology of deoxynivalenol and its acetylated and modified forms

Abstract

Mycotoxins are the most frequently occurring natural contaminants in human and animal diet. Among them, deoxynivalenol (DON), produced by Fusarium, is one of the most prevalent and thus represents an important health risk. Recent detection methods revealed new mycotoxins and new molecules derivated from the "native" mycotoxins. The main derivates of DON are the acetylated forms produced by the fungi (3- and 15-acetyl-DON), the biologically "modified" forms produced by the plant (deoxynivalenol-3-β-D-glucopyranoside), or after bacteria transformation (de-epoxy DON, 3-epi-DON and 3-keto-DON) as well as the chemically "modified" forms (norDON A-C and DON-sulfonates). High proportions of acetylated and modified forms of DON co-occur with DON, increasing the exposure and the health risk. DON and its acetylated and modified forms are rapidly absorbed following ingestion. At the molecular level, DON binds to the ribosome, induces a ribotoxic stress leading to the activation of MAP kinases, cellular cell-cycle arrest and apoptosis. The toxic effects of DON include emesis and anorexia, alteration of intestinal and immune functions, reduced absorption of the nutrients as well as increased susceptibility to infection and chronic diseases. In contrast to DON, very little information exists concerning the acetylated and modified forms; some can be converted back to DON, their ability to bind to the ribosome and to induce cellular effects varies according to the toxin. Except for the acetylated forms, their toxicity and impact on human and animal health are poorly documented.

The Food Contaminant Deoxynivalenol Exacerbates the Genotoxicity of Gut Microbiota

“…There is overwhelming evidence that DON induces a systemic and intestinal inflammatory response at both the systemic and intestinal levels (33–35). Through this inflammatory effect, DON may predispose the gut epithelium to DNA damage.…”

Strategies and Methodologies for Developing Microbial Detoxification Systems to Mitigate Mycotoxins

“…Some alternative approaches for using large animals in toxicity testing have been devised recently. For example, explants of specific and more sensitive tissues were developed by the Oswald group using pig jejunal explants to investigate the toxicity of deepoxy-DON and 3- epi -DON [139,140]. …”

“…For example, the reduction in DON toxicity due to C3 carbon epimerization was attributed to attenuated binding of 3- epi -DON within the ribosomal peptidyl transferase center [139,140], in addition to increased polarity of 3 - epi -DON and decreased molecular interactions with different cellular targets, such as Fusarium graminearum Tri101 acetyltransferase [145]. Similar results were also obtained for deepoxy-DON when transformed anaerobically by strain BBSH 797 [139,140]. This mechanistic information is pivotal for predicting how the final biotransformation product(s) will behave under different scenarios and usage conditions, such as under unfavorable pH conditions, or in the presence of metabolizing bacteria in the animal intestinal tract.…”

“…The introduction of state-of-the-art research tools, such as next-generation sequencing, recombinant-enzyme overexpression and robust HPLC-MS/MS systems, combined with our enhanced understanding of the actual mechanisms underlying the diminished toxicity of final biotransformation products [140,146,172], will immensely aid in the identification [12], optimization and usage [170,171] of such naturally-derived alternatives. It is anticipated that these novel approaches will form the basis for sustainable long-term solutions to the ever-growing problem of mycotoxins in the coming years.…”

The enzymatic detoxification of the mycotoxin deoxynivalenol: identification of DepA from the DON epimerization pathway

“…More importantly, DON has negative consequences on both human and animal health, (Streit et al ., 2013; Hassan et al ., 2015) causing gastrointestinal issues especially in mono‐gastric animals (Pestka, 2010a). Acute exposure leads to emesis associated with a total loss of appetite (Rotter et al ., 1996) while long‐term exposure leads to lack of weight gain, reduced immunity and increased sensitivity towards disease (Pestka, 2010b; Streit et al ., 2013; Payros et al ., 2016). Furthermore, DON contamination is widespread within the cereal industry with reports showing its presence in 55% of samples tested (Streit et al ., 2013).…”