Blood-Brain Barrier Effects of the Fusarium Mycotoxins Deoxynivalenol, 3 Acetyldeoxynivalenol, and Moniliformin and Their Transfer to the Brain

Behrens, Matthias; Hüwel, Sabine; Galla, Hans‐Joachim; Humpf, Hans‐Ulrich

doi:10.1371/journal.pone.0143640

Cited by 46 publications

(45 citation statements)

References 52 publications

(81 reference statements)

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“…Several mechanisms have been proposed to contribute to the reduction in feed intake induced by DON-contaminated feed. Some studies have shown that DON can cross the blood-brain barrier, leading to activation of central structures and affecting glial cell viability and function (Behrens et al 2015;Razafimanjato et al 2011). Other experiments have suggested a DONinduced reduction in plasma insulin-like growth factor acid-labile subunit (IGFALS) (Flannery et al 2013) and an increased pro-inflammatory cytokine expression (Pestka and Amuzie 2008), effects that initiate anorexia and poor growth performance.…”

Section: Discussionmentioning

confidence: 99%

Effects and biotransformation of the mycotoxin deoxynivalenol in growing pigs fed with naturally contaminated pelleted grains with and without the addition of Coriobacteriaceum DSM 11798

Sayyari

Fæste

Hansen

et al. 2018

Food Additives & Contaminants: Part A

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Deoxynivalenol (DON) is one of the most prevalent Fusarium mycotoxins in grain and can cause economic losses in pig farming due to reduced feed consumption and lower weight gains. Biodetoxification of mycotoxins using bacterial strains has been a focus of research for many years. However, only a few in vivo studies have been conducted on the effectiveness of microbial detoxification of fusariotoxins. This study was therefore aimed at investigating the effect of a feed additive containing the bacterial strain Coriobacteriaceum DSM 11798 (the active ingredient in Biomin® BBSH 797) on growth performance and blood parameters, as well as uptake and metabolism of DON, in growing pigs. Forty-eight crossbred (Landrace-Yorkshire/Duroc-Duroc) weaning pigs were fed with pelleted feed made from naturally contaminated oats, with DON at four concentration levels: (1) control diet (DON < 0.2 mg kg), (2) low-contaminated diet (DON = 0.92 mg kg), (3) medium-contaminated diet (DON = 2.2 mg kg) and (4) high-contaminated diet (DON = 5.0 mg kg) and equivalent diets containing DSM 11798 as feed additive. During the first 7 days of exposure, pigs in the highest-dose group showed a 20-28% reduction in feed intake and a 24-34% reduction in weight gain compared with pigs in the control and low-dose groups. These differences were levelled out by study completion. Towards the end of the experiment, dose-dependent reductions in serum albumin, globulin and total serum protein were noted in the groups fed with DON-contaminated feed compared with the controls. The addition of DSM 11798 had no effect on the DON-related clinical effects or on the plasma concentrations of DON. The ineffectiveness of the feed additive in the present study could be a consequence of its use in pelleted feed, which might have hindered its rapid release, accessibility or detoxification efficiency in the pig's gastrointestinal tract.

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Section: Discussionmentioning

confidence: 99%

Effects and biotransformation of the mycotoxin deoxynivalenol in growing pigs fed with naturally contaminated pelleted grains with and without the addition of Coriobacteriaceum DSM 11798

Sayyari

Fæste

Hansen

et al. 2018

Food Additives & Contaminants: Part A

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“…Cellular viability was tested after treatment for 48 h using the CCK-8 assay, like applied for the cell lines but with minor modifications. Based on earlier protocols [ 16 , 22 ] for the cultivation of PBCEC, the cryopreserved PBCEC were thawed at 37°C in a water bath, gently resuspended in culture medium (Medium 199 Earle’s with 100 U/mL penicillin, 100 μg/mL streptomycin, 100 μg/mL gentamycin, 4.1 mM l -glutamine and 10% fetal calf serum) and centrifugated at 220 × g at 20°C for 10 min. After removal of the supernatant, fresh complete medium was added and the cell pellet was resuspended twice and diluted to desired cell density.…”

Section: Methodsmentioning

confidence: 99%

“…Such TEER values are often not attained by other in vitro- cell culture models that are applied for transport studies. This property of the PBCEC is close to the in vivo -situation and ensures the tightness and reliability of a barrier system to study transport characteristics [ 16 , 20 , 22 ]. In order to assess the possibility of ENNs reaching the brain, the transport kinetics of ENN B and B1 were evaluated using this in vitro -cell culture system based on PBCEC mimicking the BBB.…”

Section: Introductionmentioning

confidence: 96%

Transport of enniatin B and enniatin B1 across the blood-brain barrier and hints for neurotoxic effects in cerebral cells

et al. 2018

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Enniatins are common contaminants of food and feed and belong to the group of the “emerging” mycotoxins, which are produced by various Fusarium species. Although a wide range of toxic effects, like antibacterial, antifungal, insecticidal and cytotoxic properties, have been described in vitro, so far, no cases of mycotoxicosis connected to enniatins in vivo are reported. Among this group of mycotoxins, enniatin B and enniatin B1 are the most prevalent compounds and therefore are present in the human diet. Enniatins can reach systemic circulation, thus, the investigation of possible neurotoxic effects is of importance. Different cerebral cells were used to address effects on cell death having an impact on the blood-brain barrier. The influence of enniatin B and enniatin B1 on cellular viability was examined via Cell Counting kit-8 assay (CCK-8) in three different cell types of the blood-brain barrier: porcine brain capillary endothelial cells (PBCEC), human brain microvascular endothelial cells (HBMEC) and human astrocytoma cells (CCF-STTG1). CCF-STTG1 cells were more sensitive to enniatin B (IC50 = 8.9 μM) and enniatin B1 (IC50 = 4.4 μM) than both endothelial cell types. In CCF-STTG1 cells, caspase-3 activation and lactate dehydrogenase (LDH) release were evaluated. Both compounds did not induce any LDH release and only enniatin B increased caspase-3 activity as a marker for apoptosis. The transport kinetics of enniatin B and enniatin B1 across the blood-brain barrier in vitro were evaluated using PBCEC, cultivated on Transwell® filter inserts. Analysis of the apical and the basolateral compartment by high performance liquid chromatography-mass spectrometry revealed high influx rates for enniatin B and enniatin B1. Thus, both compounds can reach the brain parenchyma where neurotoxic effects cannot be ruled out.

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“…MON did not affect intestinal nor blood capillary integrity in vitro. However, in vitro studies suggest that the molecule can pass the blood brain barrier [ 59 , 106 ]. After single oral gavage, 42% of the administered MON was excreted in the urine of rats within 24 h post administration, and less than 1% was excreted in the feces.…”

Section: Moniliforminmentioning

confidence: 99%

Emerging Fusarium and Alternaria Mycotoxins: Occurrence, Toxicity and Toxicokinetics

Fraeyman

Croubels

Devreese

et al. 2017

Toxins

232

172

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Emerging Fusarium and Alternaria mycotoxins gain more and more interest due to their frequent contamination of food and feed, although in vivo toxicity and toxicokinetic data are limited. Whereas the Fusarium mycotoxins beauvericin, moniliformin and enniatins particularly contaminate grain and grain-based products, Alternaria mycotoxins are also detected in fruits, vegetables and wines. Although contamination levels are usually low (µg/kg range), higher contamination levels of enniatins and tenuazonic acid may occasionally occur. In vitro studies suggest genotoxic effects of enniatins A, A1 and B1, beauvericin, moniliformin, alternariol, alternariol monomethyl ether, altertoxins and stemphyltoxin-III. Furthermore, in vitro studies suggest immunomodulating effects of most emerging toxins and a reproductive health hazard of alternariol, beauvericin and enniatin B. More in vivo toxicity data on the individual and combined effects of these contaminants on reproductive and immune system in both humans and animals is needed to update the risk evaluation by the European Food Safety Authority. Taking into account new occurrence data for tenuazonic acid, the complete oral bioavailability, the low total body clearance in pigs and broiler chickens and the limited toxicity data, a health risk cannot be completely excluded. Besides, some less known Alternaria toxins, especially the genotoxic altertoxins and stemphyltoxin III, should be incorporated in risk evaluation as well.

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Blood-Brain Barrier Effects of the Fusarium Mycotoxins Deoxynivalenol, 3 Acetyldeoxynivalenol, and Moniliformin and Their Transfer to the Brain

Cited by 46 publications

References 52 publications

Effects and biotransformation of the mycotoxin deoxynivalenol in growing pigs fed with naturally contaminated pelleted grains with and without the addition of Coriobacteriaceum DSM 11798

Effects and biotransformation of the mycotoxin deoxynivalenol in growing pigs fed with naturally contaminated pelleted grains with and without the addition of Coriobacteriaceum DSM 11798

Transport of enniatin B and enniatin B1 across the blood-brain barrier and hints for neurotoxic effects in cerebral cells

Emerging Fusarium and Alternaria Mycotoxins: Occurrence, Toxicity and Toxicokinetics

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