Blood-brain barrier transport kinetics of the cyclic depsipeptide mycotoxins beauvericin and enniatins

Taevernier, Lien; Bracke, Nathalie; Veryser, Lieselotte; Wynendaele, Evelien; Gevaert, Bert; Peremans, Kathelijne; Spiegeleer, Bart De

doi:10.1016/j.toxlet.2016.06.1741

Cited by 19 publications

(17 citation statements)

References 54 publications

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“…Many combinations of different methodologies have been carried out for mycotoxin extraction from solid biological samples namely tissues and organs. LLE techniques have been performed with several solvents; ACN and ACN-H 2 O were used for BEA and ENs extraction from mice samples including liver, kidney, colon, fat, brain, muscle, tumor, urine, and serum [ 26 , 115 ]. Masked and conjugated forms of DON and ZON were extracted using ACN/formic acid (99/1) from several rat samples including plasma, urine, liver, kidney, bladder, spleen, lung, stomach, small intestine, and large intestine [ 116 ].…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, BEA and ENs crossed the blood-brain barrier in mice exerting a high initial brain influx rate and reaching mainly the brain parenchyma (95%) after their penetration, with negligible efflux after 15 min of intra-cerebroventricular injection. Therefore, BEA and ENs are able to reach systemic circulation through various routes of exposure and may exert central nervous system (CNS) effects passing the blood-brain barrier (BBB) [ 115 ].…”

Section: Resultsmentioning

confidence: 99%

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Studies on the Presence of Mycotoxins in Biological Samples: An Overview

Escrivá¹,

Font²,

Manyes³

et al. 2017

Toxins

113

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Mycotoxins are fungal secondary metabolites with bioaccumulation levels leading to their carry-over into animal fluids, organs, and tissues. As a consequence, mycotoxin determination in biological samples from humans and animals has been reported worldwide. Since most mycotoxins show toxic effects at low concentrations and considering the extremely low levels present in biological samples, the application of reliable detection methods is required. This review summarizes the information regarding the studies involving mycotoxin determination in biological samples over the last 10 years. Relevant data on extraction methodology, detection techniques, sample size, limits of detection, and quantitation are presented herein. Briefly, liquid-liquid extraction followed by LC-MS/MS determination was the most common technique. The most analyzed mycotoxin was ochratoxin A, followed by zearalenone and deoxynivalenol—including their metabolites, enniatins, fumonisins, aflatoxins, T-2 and HT-2 toxins. Moreover, the studies were classified by their purpose, mainly focused on the development of analytical methodologies, mycotoxin biomonitoring, and exposure assessment. The study of tissue distribution, bioaccumulation, carry-over, persistence and transference of mycotoxins, as well as, toxicokinetics and ADME (absorption, distribution, metabolism and excretion) were other proposed goals for biological sample analysis. Finally, an overview of risk assessment was discussed.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Studies on the Presence of Mycotoxins in Biological Samples: An Overview

Escrivá¹,

Font²,

Manyes³

et al. 2017

Toxins

113

View full text Add to dashboard Cite

show abstract

“…The determination of ENNA, ENNA1, ENNB, ENNB1, and BEA has been carried out in urine [14][15][16][17][18][19], and serum [14][15][16]18,[20][21][22][23][24], from both humans and animals, but also in feces samples [15,16,18] and in different organs and tissues from animals [25][26][27][28]. The vast majority of these analytical methods are based on LC-MS/MS, although LC coupled to high resolution mass spectrometry (HRMS) has also been proposed [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Dispersive Solid-Phase Extraction using Magnetic Carbon Nanotube Composite for the Determination of Emergent Mycotoxins in Urine Samples

Arroyo‐Manzanares

Peñalver-Soler

Campillo

et al. 2020

Toxins

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Dispersive magnetic solid-phase extraction (DMSPE) has received growing attention for sample treatment preconcentration prior to the separation of analytes due to its many advantages. In the present work, the potential of DMSPE for the determination of emergent mycotoxins (enniatins A, A1, B and B1, and beauvericin) is investigated for the first time. Different magnetic nanoparticles were tested and a magnetic multiwalled carbon nanotube (Fe3O4@MWCNT) composite was selected for the extraction and preconcentration of the five target mycotoxins in human urine samples before their analysis by ultrahigh performance liquid chromatography coupled to high resolution mass spectrometry (UHPLC-HRMS). The nanocomposite was characterized by energy dispersive X-ray spectrometry, scanning electron microscopy, Fourier transform infrared spectrophotometry, and X-ray diffraction. Several parameters affecting the adsorption and desorption of DMSPE steps were optimized and the method was fully validated. Due to a matrix effect, matrix-matched calibration curves were necessary to carry out quantification. In this way, limits of quantification of between 0.04 and 0.1 μg/L, relative standard deviation values lower than 12% and recoveries between 89.3% and 98.9% were obtained. Finally, a study of the reuse of the Fe3O4@MWCNT composite was carried out, confirming that it can be reused at least four times.

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“…This study was conducted over the course of 100 minutes. The results of this short time in vivo- mouse study, indicate a high and rapid influx into the brain with distribution to the brain parenchyma [ 14 ].Our study aims to add more insights to the kinetics of the transfer of ENNs with a longer exposure time (48 h) and eight sampling times over the course of the experiment. Thus, a better kinetic profile can be shown.…”

Section: Introductionmentioning

confidence: 99%

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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Blood-brain barrier transport kinetics of the cyclic depsipeptide mycotoxins beauvericin and enniatins

Cited by 19 publications

References 54 publications

Studies on the Presence of Mycotoxins in Biological Samples: An Overview

Studies on the Presence of Mycotoxins in Biological Samples: An Overview

Dispersive Solid-Phase Extraction using Magnetic Carbon Nanotube Composite for the Determination of Emergent Mycotoxins in Urine Samples

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

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