Zearalenone

Interaction of mycotoxin zearalenone with human serum albumin.[Pubmed:28365492]

J Photochem Photobiol B. 2017 May;170:16-24.

Zearalenone (ZEN) is a mycotoxin produced mainly by Fusarium species. Fungal contamination of cereals and plants can result in the formation of ZEN, leading to its presence in different foods, animal feeds, and drinks. Because ZEN is an endocrine disruptor, it causes reproductive disorders in farm animals and hyperoestrogenic syndromes in humans. Despite toxicokinetic properties of ZEN were studied in more species, we have no information regarding the interaction of ZEN with serum albumin. Since albumin commonly plays an important role in the toxicokinetics of different toxins, interaction of ZEN with albumin has of high biological importance. Therefore the interaction of ZEN with human serum albumin (HSA) was investigated using spectroscopic methods, ultrafiltration, and molecular modeling studies. Fluorescence spectroscopic studies demonstrate that ZEN forms complex with HSA. Binding constant (K) of ZEN-HSA complex was quantified with fluorescence quenching technique. The determined binding constant (logK=5.1) reflects the strong interaction of ZEN with albumin suggesting the potential biological importance of ZEN-HSA complex formation. Based on the results of the investigations with site markers as well as docking studies, ZEN occupies a non-conventional binding site on HSA. Considering the above listed observations, we should keep in mind this interaction if we would like to precisely understand the toxicokinetic behavior of ZEN.

Adsorption of aflatoxin B1, zearalenone and ochratoxin A by microorganisms isolated from Kefir grains.[Pubmed:28376398]

Int J Food Microbiol. 2017 Jun 19;251:1-7.

A strategy to reduce the deleterious effects of mycotoxins is to use dietary supplements that contain microorganisms that bind mycotoxins and decrease their gastrointestinal absorption. Novel strains were isolated from a Kefir culture and assessed for their mycotoxin adsorption and biotransformation ability. The most active strains were identified using DNA sequencing, and the stability of microorganism/mycotoxin complexes was evaluated using buffer solutions to simulate the pH conditions in the gastrointestinal tract. Our results showed that the microorganism consortium of Kefir grains adsorbed 82 to 100% of aflatoxin B1 (AFB1), Zearalenone (ZEA) and ochratoxin A (OTA) when cultivated in milk. The main strains that were capable of mycotoxin adsorption were identified as Lactobacillus kefiri, Kazachstania servazzii and Acetobacter syzygii. The strain L. kefiri KFLM3 was the most active, adsorbing 80 to 100% of the studied mycotoxins when cultivated in milk. Nonetheless, the strain K. servazzii KFGY7 retained more mycotoxin after the desorption experiments (65, 69 and 67% for AFB1, OTA and ZEA, respectively). These findings suggest that Kefir consumption may help to reduce gastrointestinal absorption of these mycotoxins and consequently reduce their toxic effects. The isolated strains may be of interest for the development of fermented dairy products for human consumption that have a new probiotic characteristic, the adsorption of mycotoxins.

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.[Pubmed:28287437]

Toxins (Basel). 2017 Mar 10;9(3). pii: toxins9030098.

The enteric nervous system (ENS) can undergo adaptive and reparative changes in response to physiological and pathological stimuli. These manifest primarily as alterations in the levels of active substances expressed by the enteric neuron. While it is known that mycotoxins can affect the function of the central and peripheral nervous systems, knowledge about their influence on the ENS is limited. Therefore, the aim of the present study was to investigate the influence of low doses of Zearalenone (ZEN) and T-2 toxin on calcitonin gene related peptide-like immunoreactive (CGRP-LI) neurons in the ENS of the porcine descending colon using a double immunofluorescence technique. Both mycotoxins led to an increase in the percentage of CGRP-LI neurons in all types of enteric plexuses and changed the degree of co-localization of CGRP with other neuronal active substances, such as substance P, galanin, nitric oxide synthase, and cocaine- and amphetamine-regulated transcript peptide. The obtained results demonstrate that even low doses of ZEN and T-2 can affect living organisms and cause changes in the neurochemical profile of enteric neurons.

Effects of Electron Beam Irradiation on Zearalenone and Ochratoxin A in Naturally Contaminated Corn and Corn Quality Parameters.[Pubmed:28264463]

Toxins (Basel). 2017 Feb 27;9(3). pii: toxins9030084.

Zearalenone (ZEN) and ochratoxin A (OTA) are secondary toxic metabolites widely present in grains and grain products. In this study, the effects of electron beam irradiation (EBI) on ZEN and OTA in corn and the quality of irradiated corn were investigated. Results indicated that EBI significantly affected ZEN and OTA. The degradation rates of ZEN and OTA at 10 kGy in solution were 65.6% and 75.2%, respectively. The initial amounts significantly affected the degradation rate. ZEN and OTA in corn were decreased by the irradiation dose, and their degradation rates at 50 kGy were 71.1% and 67.9%, respectively. ZEN and OTA were more easily degraded in corn kernel than in corn flour. Moisture content (MC) played a vital role in ZEN and OTA degradation. High MC was attributed to high ZEN and OTA degradation. The quality of irradiated corn was evaluated on the basis of irradiation dose. L* value changed, but this change was not significant (p > 0.05). By contrast, a* and b* decreased significantly (p < 0.05) with irradiation dose. The fatty acid value increased significantly. The pasting properties, including peak, trough, breakdown, and final and setback viscosities, were also reduced significantly (p < 0.05) by irradiation. Our study verified that EBI could effectively degrade ZEN and OTA in corn. Irradiation could also affect corn quality.

Effects of zearalenone and alpha-Zearalenol in comparison with Raloxifene on T47D cells.[Pubmed:19730705]

Toxicol Mech Methods. 2009 Mar;19(3):246-50.

Zearalenone (Zen) is a mycotoxin with estrogenic effect which contaminates cereals. In cell culture, Zen and its metabolite, alpha-Zearalenol (alpha-Zel), stimulate breast cancer cells growth. Today hormone-dependent cancers are important because of high incidence and death rate. Previous studies showed that Zen and alpha-Zel have an effect on hormone-dependent cancers. This study explains the effects of the mentioned compounds in comparison with Raloxifene as an anti-estrogen. Cell culture technique was used with MDA-MB-231 and T47D cells for evaluation of compounds. MDA-MB-231 cells were used as negative control and also for proving that treatment compounds merely affect, due to their proliferation activity in the applied doses. According to the Resazurine-based method, for toxicity assay, none of the test compounds have an effect on MDA-MB-231 cells but do effect the growth of T47D cells. Zen and alpha-Zel at low concentrations (10-8-10-9 M) stimulated T47D cell growth and Raloxifene strongly inhibited cell growth induced by Zen and alpha-Zel. There is a noticeable result in controlling diet of hormonal carcinogenic compounds and applying novel anti-estrogens for prevention and treatment of hormone-dependent cancers.

Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta.[Pubmed:9751507]

Endocrinology. 1998 Oct;139(10):4252-63.

The rat, mouse and human estrogen receptor (ER) exists as two subtypes, ER alpha and ER beta, which differ in the C-terminal ligand-binding domain and in the N-terminal transactivation domain. In this study, we investigated the estrogenic activity of environmental chemicals and phytoestrogens in competition binding assays with ER alpha or ER beta protein, and in a transient gene expression assay using cells in which an acute estrogenic response is created by cotransfecting cultures with recombinant human ER alpha or ER beta complementary DNA (cDNA) in the presence of an estrogen-dependent reporter plasmid. Saturation ligand-binding analysis of human ER alpha and ER beta protein revealed a single binding component for [3H]-17beta-estradiol (E2) with high affinity [dissociation constant (Kd) = 0.05 - 0.1 nM]. All environmental estrogenic chemicals [polychlorinated hydroxybiphenyls, dichlorodiphenyltrichloroethane (DDT) and derivatives, alkylphenols, bisphenol A, methoxychlor and chlordecone] compete with E2 for binding to both ER subtypes with a similar preference and degree. In most instances the relative binding affinities (RBA) are at least 1000-fold lower than that of E2. Some phytoestrogens such as coumestrol, genistein, apigenin, naringenin, and kaempferol compete stronger with E2 for binding to ER beta than to ER alpha. Estrogenic chemicals, as for instance nonylphenol, bisphenol A, o, p'-DDT and 2',4',6'-trichloro-4-biphenylol stimulate the transcriptional activity of ER alpha and ER beta at concentrations of 100-1000 nM. Phytoestrogens, including genistein, coumestrol and Zearalenone stimulate the transcriptional activity of both ER subtypes at concentrations of 1-10 nM. The ranking of the estrogenic potency of phytoestrogens for both ER subtypes in the transactivation assay is different; that is, E2 >> Zearalenone = coumestrol > genistein > daidzein > apigenin = phloretin > biochanin A = kaempferol = naringenin > formononetin = ipriflavone = quercetin = chrysin for ER alpha and E2 >> genistein = coumestrol > Zearalenone > daidzein > biochanin A = apigenin = kaempferol = naringenin > phloretin = quercetin = ipriflavone = formononetin = chrysin for ER beta. Antiestrogenic activity of the phytoestrogens could not be detected, except for Zearalenone which is a full agonist for ER alpha and a mixed agonist-antagonist for ER beta. In summary, while the estrogenic potency of industrial-derived estrogenic chemicals is very limited, the estrogenic potency of phytoestrogens is significant, especially for ER beta, and they may trigger many of the biological responses that are evoked by the physiological estrogens.

Zearalenone is a mycotoxin produced mainly by fungi belonging to the genus Fusarium in foods and feeds. Possess oestrogenic activity in pigs, cattle and sheep, with low acute toxicity. Causes precocious development of mammae and other estrogenic effects in young gilts.

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