Abstract
The mycotoxin zearalenone (ZEN), which frequently contaminates cereal-based human food and animal feed, is known to have an estrogenic effect. The biological response associated with exposure to ZEN has rarely been reported in organs other than the reproductive system. In the intestine, several studies suggested that ZEN might stimulate molecular changes related to the activation of early carcinogenesis, but the molecular mechanisms behind these events are not yet known. In this study, we investigated gene expression and changes in protein abundance induced by acute exposure to ZEN in the jejunum of castrated male pigs using an explant model. Our results indicate that ZEN induces the accumulation of ERα but not ERβ, modulates Wnt/β-catenin and TGF-β signaling pathways, and induces molecular changes linked with energy sensing and the antimicrobial activity without inducing inflammation. Our results confirm that the intestine is a target for ZEN, inducing changes that promote cellular proliferation and could contribute to the onset of intestinal pathologies.
Highlights
Zearalenone (ZEN) is a mycotoxin synthesized by some fungi of the Fusarium genus that frequently contaminate crops such as corn, barley, wheat, rice, oats, and sorghum, in temperate regions [1]
At the cellular and molecular level, several reports have described changes in the gene expression of pro-inflammatory cytokines, genes implicated in the induction of a proliferative state such as Dickkopf-related protein 1 (DKK1), β-catenin or the proto-oncogene c-Myc [8,12,30]. These results suggest that ZEN can induce transient proliferation in the small intestinal crypt, which could be connected with pro-cancerogenic changes in wingless-type MMTV integration site family (Wnt)/β-catenin and transforming growth factor β (TGF-β) signaling pathways
We investigated the activation/repression of Wnt/β-catenin and TGF-β signaling pathways, the immune status and metabolism by ZEN to understand the effect of this toxin on the intestine of castrated male pigs
Summary
Zearalenone (ZEN) is a mycotoxin synthesized by some fungi of the Fusarium genus that frequently contaminate crops such as corn, barley, wheat, rice, oats, and sorghum, in temperate regions [1]. ZEN is classified as an endocrine disruptor because it can bind and activate estrogen receptors with hyper-estrogenic effects [2]. ZEN provokes a dose-dependent increase of reactive oxygen species levels, oxidative DNA damage, alteration of the mitochondria, membrane disruption and lipid peroxidation [4,5,6,7]. These processes can activate a pro-inflammatory cascade [8,9], resulting in the expression of inflammatory cytokines, which has been reported in several tissues exposed to ZEN [9,10,11]. The in vitro toxic effect of Toxins 2020, 12, 113; doi:10.3390/toxins12020113 www.mdpi.com/journal/toxins
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