Zearalenone-induced changes in the lymphoid tissue and mucosal nerve fibers in the porcine ileum

Abstract

This is the first study to examine zearalenone-(ZEN) induced changes in the immune system of the ileum and substance P-(SP-) and vasoactive intestinal peptide-(VIP-) immunoreactive nerve fibers in the mucosa, which participate in the regulation of intestinal functions under physiological conditions and during pathological processes. The aim of this study was also to identify potential relationships between selected immune and neural elements in ileal Peyer's patches in pigs that were and were not exposed to ZEN. The experiment was performed on 10 prepubertal gilts divided into two groups: the experimental group (n=5) where ZEN was administered at 0.1 mg kg -1 feed day -1 for 42 days, and the control group (n=5) which was administered a placebo. The tissue levels of cytokines were determined by enzyme-linked immunosorbent assay which revealed elevated concentrations of IL-12/23 40p and IL-1 β in animals exposed to ZEN. Flow cytometry revealed a lower percentage of CD21+ lymphocytes in pigs exposed to ZEN in comparison with control animals. The tissue levels of neuropeptides were evaluated in the dot blot procedure which demonstrated higher concentrations of VIP and SP in experimental pigs. In experimental animals, numerous VIP-like immunoreactive processes were observed, and SP-immunoreactive nerve fibers formed a very dense network. Our results demonstrate for the first time that ZEN can modify the chemical coding of nerve structures in the gastrointestinal system. Those modifications can be attributed to ZEN's impact on estrogen receptors or its pro-inflammatory properties, and they reflect changes that take place in the nervous system at the transcriptional, translational and metabolic level.

The Influence of Low Doses of Zearalenone and T-2 Toxin on Calcitonin Gene Related Peptide-Like Immunoreactive (CGRP-LI) Neurons in the ENS of the Porcine Descending Colon

“…Two facts confirm this supposition. Firstly, it is well known that the expression of neuroprotective factors in the ENS increases during pathological processes [5,6,42,43], and the growth of CGRP-like immunoreactivity has been observed during both the present study and in previous investigations on other fragments of the digestive tract [44]. Secondly, CGRP affects the release of nitric oxide, whose neuroprotective activity is relatively well surveyed [45,46,47].…”

“…Moreover, it can lead to developmental disorders, stunted growth, renal failure, and blood clots [4,5]. ZEN also harms the digestive system by causing cell proliferation and inflammation of the intestinal mucosal layer [5,6]. Previous studies have also shown the negative effects of ZEN on the nervous system, which are related to the presence of estrogen receptors in the brain and the fact that phytoestrogens are able to cross the blood-brain barrier [7,8].…”

“…These mechanisms of action may in turn impact the ENS [27]. The knowledge connected with the influence of low doses of mycotoxins on enteric neurons is fragmentary and incomplete [5,6,13], although it is known that the ENS is able to undergo structural, functional or chemical changes as a result of adaptive or reparative processes in response to various pathological and toxicological agents [13,28]. The impact of ZEN and T-2 toxin on CGRP distribution in the ENS has not been studied at all, even though this peptide seems to be an important neuronal factor involved in regulatory processes linked to estrogenic and/or immunological activity [29,30].…”

Appropriateness to set a group health‐based guidance value for zearalenone and its modified forms

“…According to the authors, this is the first report demonstrating that ZEN affects nerve fibres in the digestive tract at low dose. Obremski et al (2015a) fed prepubertal gilts (aged 2 months) with diets containing 0.1 mg ZEN/kg feed in gelatine capsules for 42 days (corresponding to a dose of 5 lg ZEN/kg bw per day). After that, ileal Peyer's patch (IPP) samples were prepared and used for analyses.…”

Identification of neuropeptide Y in superior cervical ganglion neurons that project to the oesophagus – A combined immunohistochemical labelling and retrograde tracing study in pigs

“…It is known that the oesophagus may receive innervation from jugularnodose, sphenopalatine, stellate and dorsal root ganglia (Yu et al, 2015), but the major adrenergic innervation of this part of the GI tract derives from the superior cervical ganglia (Wojtkiewicz et al, 2011;Juranek and Wojtkiewicz, 2015). To date, a wide range of active substances have been noted both in the ENS and extrinsic innervation (Majewski et al, 2002;Obremski et al, 2015;Rytel and Calka, 2016;Szymanska et al, 2018), including neuropeptide Y (NPY).…”