The role of the gut microbiota in toxicity and risk assessment of masked Fusarium mycotoxins

Abstract

General introduction | 1115-acetyl-DON induced the production of IL-8 cytokine, and based on the production of IL-8, the toxicity could be ranked as 3-acetyl-DON < DON < 15-acetyl-DON (Kadota et al., 2013).It has been suggested that the toxicity of 15-acetyl-DON is higher than that of DON, while the toxicity of 3-acetyl-DON is comparable, lower or higher than that of DON, depending on the toxicity test and endpoint quantified. Furthermore, 3-or 15-acetyl-DON and DON demonstrated similar effects on induction of food refusal, growth retardation, and emesis in animal models (Forsell et al., 1987; Abbas et al., 1986). Wu et al. (2012) conducted an anorexia induction bioassay, and proved that acetyl-DONs both induced feed refusal at a level comparable to that induced by DON. In the mink emesis model, the effective doses resulting in emetic events in 50% of the minks upon oral exposure to DON, 3-acetyl-DON and 15-acetyl-DON were 30, 290 and 40 µg/kg bw, respectively. In this model, the mink showed a longer latency for emetic effects upon exposure to 3-acetyl-DON as compared to DON and 15-acetyl-DON which may be ascribed to the time needed for conversion of 3-acetyl-DON to DON in the digestive tract (Wu et al., 2013). ADME of DON and acetylated DONsADME represents the absorption (A), distribution (D), metabolism (M) and elimination (E) of compounds in an organism. The absorption of DON following oral intake is rapid. In 15-30 min, the absorption percentage varies from 7% in ruminants (sheep and cow) to 25% in rat, and up to 89% in pig Goyarts et al., 2006). The oral bioavailability of DON is lowest in poultry, and this may be related to the low sensitivity of poultry to DON . Compared to male mice, female mice have a higher absorption (Wan et al., 2013). Upon absorption DON can be metabolized in the intestinal or liver tissue to different conjugates before being transferred to the systemic circulation. Via the systemic circulation DON and its metabolites are rapidly distributed to all tissues (Rotter at al., 1991).DON and its metabolites can be present in urine and feces. The clearance of DON is rather rapid in most animal species, as illustrated by the fact that upon intravenous administration of DON to pig plasma the half-time for elimination was 3.9 h (Rotter et al., 1991). The excretion of DON and its metabolites could be described by a two-compartment kinetic model