Abstract
The few data available on fusarenon-X (FX) do not support the derivation of health-based guidance values, although preliminary results suggest higher toxicity than other regulated trichothecenes. Using histo-morphological analysis and whole transcriptome profiling, this study was designed to obtain a global view of the intestinal alterations induced by FX. Deoxynivalenol (DON) served as a benchmark. FX induced more severe histological alterations than DON. Inflammation was the hallmark of the molecular toxicity of both mycotoxins. The benchmark doses for the up-regulation of key inflammatory genes by FX were 4- to 45-fold higher than the previously reported values for DON. The transcriptome analysis revealed that both mycotoxins down-regulated the peroxisome proliferator-activated receptor (PPAR) and liver X receptor - retinoid X receptor (LXR-RXR) signaling pathways that control lipid metabolism. Interestingly, several pathways, including VDR/RXR activation, ephrin receptor signaling, and GNRH signaling, were specific to FX and thus discriminated the transcriptomic fingerprints of the two mycotoxins. These results demonstrate that FX induces more potent intestinal inflammation than DON. Moreover, although the mechanisms of toxicity of both mycotoxins are similar in many ways, this study emphasize specific pathways targeted by each mycotoxin, highlighting the need for specific mechanism-based risk assessments of Fusarium mycotoxins.
Highlights
Trichothecene mycotoxins are of increasing concern with respect to food safety issues due to their frequent and global occurrence[1]
A histo-morphometric analysis was conducted on pig intestinal explants exposed to FX and its well-characterized congener DON to obtain a comparative appraisal of the tissue alterations induced by both trichothecene mycotoxins
The present study investigated the intestinal toxicity of FX compared with DON
Summary
Trichothecene mycotoxins are of increasing concern with respect to food safety issues due to their frequent and global occurrence[1]. FX-induced diarrhea has been related to an increased cyclic AMP content of the intestinal mucosa[10]. Because structurally related contaminants may co-occur, a toxic equivalency factor (TEF) can be defined to assess the combined risk[12]. This approach has been recently implemented for the Fusarium mycotoxin zearalenone and its modified forms[13] as well as for the type A trichothecenes T2 and HT2 and their modified forms[14]. The intestinal mucosa is the first barrier against ingested chemical contaminants, including mycotoxins. Following ingestion of contaminated food, the intestine is exposed to high concentrations of mycotoxins[18, 19]. Using a porcine jejunal explant model, our research group reported the ability of DON and some trichothecenes to induce severe alterations of the intestinal morphology and an inflammatory response, which could result in increased susceptibility to intestinal inflammatory diseases[20,21,22]
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