Fusarium Mycotoxins Disrupt the Barrier and Induce IL-6 Release in a Human Placental Epithelium Cell Line
Negisa Seyed ToutounchiAstrid HogenkampSoheil VarastehBelinda van’t LandJohan GarssenAletta D. KraneveldGert FolkertsSaskia Braber
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Deoxynivalenol, T-2 toxin, and zearalenone, major Fusarium mycotoxins, contaminate human food on a global level. Exposure to these mycotoxins during pregnancy can lead to abnormalities in neonatal development. Therefore, the aim of this study was to investigate the effects of Fusarium mycotoxins on human placental epithelial cells. As an in vitro model of placental barrier, BeWo cells were exposed to different concentrations of deoxynivalenol, zearalenone or T-2 toxin. Cytotoxicity, effects on barrier integrity, paracellular permeability along with mRNA and protein expression and localization of junctional proteins after exposure were evaluated. Induction of proinflammatory responses was determined by measuring cytokine production. Increasing mycotoxin concentrations affect BeWo cell viability, and T-2 toxin was more toxic compared to other mycotoxins. Deoxynivalenol and T-2 toxin caused significant barrier disruption, altered protein and mRNA expression of junctional proteins, and induced irregular cellular distribution. Although the effects of zearalenone on barrier integrity were less prominent, all tested mycotoxins were able to induce inflammation as measured by IL-6 release. Overall, Fusarium mycotoxins disrupt the barrier of BeWo cells by altering the expression and structure of junctional proteins and trigger proinflammatory responses. These changes in placental barrier may disturb the maternal-fetal interaction and adversely affect fetal development.Keywords:
Proinflammatory cytokine
Paracellular transport
Abstract Fusarium mycotoxin contamination of both foods and feeds is an inevitable phenomenon worldwide. Deoxynivalenol, nivalenol, zearalenone, T-2 toxin and fumonisin B1 are the most studied Fusarium mycotoxins. Co-contamination of mycotoxins has also been studied frequently. Fusarium mycotoxins occur frequently in foods at very low concentrations, so there is a need to provide sensitive and reliable methods for their early detection. The present review provides insight on the types, toxicology and occurrence of Fusarium mycotoxins. It further elucidates various detection methods of mycotoxin production from Fusarium strains, with a special focus on chromatographic and immunochemical techniques.
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strains of Fusarium graminearum isolated from different geographic distribution in Sichuan Province were assayed for production of mycotoxin zearalenone(ZEN)and deoxynivalenol (DON) by Heigh Performance Liquid Chromatography (HPLC).The results indicated that all the 11 strains of F.graminearum could produce mycotoxin ZEN and DON,but there were great differences in ability to produce ZEN ranging between 0.85g8.99g/g,and DON between 0027mg2899mg/g among the tested strains.The concentration of the two toxins in naturally infected wheat kernel increased with the severity of infected seeds.
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The mycotoxins zearalenone, deoxynivalenol, 3- or 15-acetyldeoxynivalenol, nivalenol, and fusarenone occurred in the kernels and cobs of five samples of corn ears affected by red ear rot in Poland in 1988. Zearalenone (0.7-350 mg/ kg) was present in all samples. Deoxynivalenol (12-208 mg/ kg), 3-acetyldeoxynivalenol (0-7.5 mg/ kg), and 15-acetyldeoxynivalenol (0-8.8 mg/kg) were detected in three samples infected with Fusarium graminearum. Nivalenol (33-56 mg/kg) and fusarenone (0.6-20 mg/ kg) were found in two samples infected with F. crookwellense. These results agree with reports on mycotoxin production by these two fungi under laboratory conditions.
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Fusarium graminearum (Schwabe) contaminates agricultural crops and commodities with trichothecenes, mostly deoxynivalenol and its acetyl-derivatives. Current techniques available to detect final mycotoxin contamination products usually require an extended time lag between sampling and the corresponding report, and include different clean-up steps and eventually derivatisation. This study was aimed to develop a methodology to detect toxigenic F. graminearum prior to mycotoxin production. Headspace solid-phase microextraction coupled to capillary gas chromatography is shown to be useful to predict the potential of trichothecene mycotoxin formation by detecting the presence of F. graminearum at early stages of fungal growth in wheat cultivars, based on the detection of trichodiene (TRI), the volatile intermediate of trichothecenes. We showed that TRI is a useful marker to detect toxigenic Fusarium in wheat spikes from live plants, regardless of the actual development of Fusarium head blight (FHB). This is the first predictive methodology for FHB and trichothecene occurrence in field-collected samples. It might be a useful tool to help to prevent the risk of mycotoxin contamination.
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Fusarium species cause not only root, stem and ear rot with severe reductions in crop yield, they produce also toxic secondary metabolites (mycotoxins) such as deoxynivalenol (DON) and zearalenone (ZEA). During several growing seasons the presence of Fusarium spp was followed up. DON and ZEA were determined and related to infection levels. The distribution of DON and ZEA in the different plant parts was studied as well as the influence of the ensiling process on the mycotoxin content. More or less important varietal differences in susceptibility for Fusarium spp. could be detected. DON and ZEA were clearly present in most of the analysed samples. No clear relationship could be detected between visual disease symptoms and mycotoxin content. The accumulation of DON and ZEA was different for the analysed aerial plant parts. The ensiling process gave no reduction of the mycotoxin content.
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Most Fusarium species are capable of producing mycotoxins that may cause adverse effects on human or animal health. The most commonly studied Fusarium mycotoxins include trichothecenes, zearalenone and fumonisins. However, it seems that nearly all of the most prevalent Fusarium species infecting grains are also capable of producing other toxic metabolites. The existing studies, although exiguous, have clearly demonstrated that other toxic metabolites of Fusarium spp. are also present in our foods and feeds, occasionally at very high levels. It is apparent that since mycotoxins, including these 'other' metabolites, are natural toxins, they cannot be completely eliminated from food and feed chains. However, scientific studies are needed to determine their true significance. Thus, the mechanism and level of toxicity as well as presence and concentration levels will have to be fully clarified. In this paper, we briefly review the prevalence of the dominant Fusarium species contaminating maize and small-grain cereals worldwide, and the current knowledge on the biological activity as well as the natural occurrence of their selected less-known toxic metabolites. Additionally, the significance of these 'other' Fusarium mycotoxins is discussed.
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