Abstract
BackgroundSecondary metabolites produced by Fusarium fungi frequently contaminate food and feed and have adverse effects on human and animal health. Fusarium mycotoxins exhibit a wide structural and biosynthetic diversity leading to different toxicokinetics and toxicodynamics. Several studies investigated the toxicity of mycotoxins, focusing on very specific targets, like the brain. However, it still remains unclear how fast mycotoxins reach the brain and if they impair the integrity of the blood-brain barrier. This study investigated and compared the effects of the Fusarium mycotoxins deoxynivalenol, 3-acetyldeoxynivalenol and moniliformin on the blood-brain barrier. Furthermore, the transfer properties to the brain were analyzed, which are required for risk assessment, including potential neurotoxic effects.MethodsPrimary porcine brain capillary endothelial cells were cultivated to study the effects of the examined mycotoxins on the blood-brain barrier in vitro. The barrier integrity was monitored by cellular impedance spectroscopy and 14C radiolabeled sucrose permeability measurements. The distribution of the applied toxins between blood and brain compartments of the cell monolayer was analyzed by high performance liquid chromatography-mass spectrometry to calculate transfer rates and permeability coefficients.ResultsDeoxynivalenol reduced the barrier integrity and caused cytotoxic effects at 10 μM concentrations. Slight alterations of the barrier integrity were also detected for 3-acetyldeoxynivalenol. The latter was transferred very quickly across the barrier and additionally cleaved to deoxynivalenol. The transfer of deoxynivalenol and moniliformin was slower, but clearly exceeded the permeability of the negative control. None of the compounds was enriched in one of the compartments, indicating that no efflux transport protein is involved in their transport.
Highlights
This study investigated and compared the effects of the Fusarium mycotoxins deoxynivalenol, 3-acetyldeoxynivalenol and moniliformin on the blood-brain barrier
This study focused on Fusarium mycotoxins frequently detected in food and feed and their potential abilities to cross the blood-brain barrier (BBB) or impair BBB integrity, which are a perquisites to whether or not they might cause adverse effects in the brain
It can be summarized that trichothecenes could cause cytotoxic effects at the BBB and reduce its integrity. 3-AcDON and MON were shown to exhibit much weaker or almost no adverse effects at the BBB in vitro
Summary
The blood-brain barrier (BBB) is a highly selective permeability barrier separating the blood stream from the interstitial fluid in the brain This barrier controls the nutrient supply for all cerebral cells and protects the highly sensitive neurons from any adverse effects caused by changes in osmotic pressure or xenobiotics as well as several endogenous compounds present in the bloodstream. The BBB mainly consists of three cell types: Endothelial cells, directly forming the cerebral microvessels to control the efflux and influx of nutrients and xenobiotics [1]. They are coated by a basal lamina, in which pericytes are located. Several studies investigated the toxicity of mycotoxins, focusing on very specific targets, like the brain. The transfer properties to the brain were analyzed, which are required for risk assessment, including potential neurotoxic effects
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