Abstract

This study demonstrates that low doses (somewhat above the No Observed Adverse Effect Level, NOAEL) of the mycoestrogen zearalenone (ZEN) and its metabolites display multispecificity towards various biological targets in gilts. The observed responses in gilts were surprising. The presence of ZEN and zearalenols (ZELs) did not evoke a response in the porcine gastrointestinal tract, which was attributed to dietary tolerance. Lymphocyte proliferation was intensified in jejunal mesenteric lymph nodes, and lymphocyte counts increased in the jejunal epithelium with time of exposure. In the distal digestive tract, fecal bacterial counts decreased, the activity of fecal bacterial enzymes and lactic acid bacteria increased, and cecal water was characterized by higher genotoxicity. The accompanying hyperestrogenism led to changes in mRNA activity of selected enzymes (cytochrome P450, hydroxysteroid dehydrogenases, nitric oxide synthases) and receptors (estrogen and progesterone receptors), and it stimulated post-translational modifications which play an important role in non-genomic mechanisms of signal transmission. Hyperestrogenism influences the regulation of the host’s steroid hormones (estron, estradiol and progesteron), it affects the virulence of bacterial genes encoding bacterial hydroxysteroid dehydrogenases (HSDs), and it participates in detoxification processes by slowing down intestinal activity, provoking energy deficits and promoting antiporter activity at the level of enterocytes. In most cases, hyperestrogenism fulfils all of the above roles. The results of this study indicate that low doses of ZEN alleviate inflammatory processes in the digestive system, in particular in the proximal and distal intestinal tract, and increase body weight gains in gilts.

Highlights

  • This article summarized the results of studies conducted in our Department in the last six years, and it makes a reference to recent scientific achievements relating to the estrogenic mycotoxin ZEN.Our studies have focused on ZEN’s multispecificity towards selected cells and tissues of the porcine gastrointestinal tract [1,2]

  • estrogen receptors (ERs) can be activated by post-translational modification, which influences non-genomic signal transduction [96], including by ZEN [97,98]

  • The described situation can have two outcomes: (i) in pre-pubertal gilts, higher energy expenditure [42] is required for the above processes to take place, which was indirectly confirmed by blood glucose levels; (ii) gilts could develop different responses to ZEN in the peripheral regions of the circulatory system where blood was sampled for metabolic tests

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Summary

Introduction

Our studies have focused on ZEN’s multispecificity towards selected cells and tissues of the porcine gastrointestinal tract [1,2]. It is a novel approach in the existing body of research [3], which so far has targeted mainly tissues with large clusters of estrogen receptors (ERs). Plant materials are widely used in the production of food and feed, and cereal products account for a large part of human and animal diets [6] For this reason, knowledge relating to pharmacokinetic processes involving mycotoxins, examined in preclinical studies, is required to guarantee the safety of food and feed products. Most studies examined the jejunum and duodenum [21,22,25]

Mode of Action in Toxicology
Low-Dose Hypothesis
Interactions as an Element of MOA
Activity of ZEN
Multispecificity and Activity of Estrogens
Activity
Interactions
Participation of Selected CYPs and HSDs
Antiporter
This could suggest that ERβ modulates ERα activity
Morphometry of the Duodenum and Jejunum
The Carryover Factor and ERs
Microbiota Diversity in the Intestinal Lumen
Genotoxicity of Cecal Water
Expression of Intestinal Nitric Oxide Synthase
Lymphocyte Subpopulations in Mesenteric Blood Vessels
Evaluation of the Metabolic Profile
Body Weight Gains
Summary—Key Events Which Play a Major Role in Clinical States
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