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

Behrens M, Hüwel S, Galla H, Humpf H

Zusammenfassung

\textless}sec id={\textquotedbl}sec001{\textquotedbl}{\textgreater} {\textless}title{\textgreater}Background{\textless}/title{\textgreater} Secondary metabolites produced by {\textless}italic{\textgreater}Fusarium{\textless}/italic{\textgreater} fungi frequently contaminate food and feed and have adverse effects on human and animal health. {\textless}italic{\textgreater}Fusarium{\textless}/italic{\textgreater} 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 {\textless}italic{\textgreater}Fusarium{\textless}/italic{\textgreater} 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.{\textless}/p{\textgreater} {\textless}/sec{\textgreater} {\textless}sec id={\textquotedbl}sec002{\textquotedbl}{\textgreater} {\textless}title{\textgreater}Methods{\textless}/title{\textgreater} Primary porcine brain capillary endothelial cells were cultivated to study the effects of the examined mycotoxins on the blood-brain barrier {\textless}italic{\textgreater}in vitro{\textless}/italic{\textgreater}. The barrier integrity was monitored by cellular impedance spectroscopy and {\textless}sup{\textgreater}14{\textless}/sup{\textgreater}C 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.{\textless}/p{\textgreater} {\textless}/sec{\textgreater} {\textless}sec id={\textquotedbl}sec003{\textquotedbl}{\textgreater} {\textless}title{\textgreater}Results{\textless}/title{\textgreater} Deoxynivalenol reduced the barrier integrity and caused cytotoxic effects at 10 muM 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.{\textless}/p{\textgreater} {\textless}/sec{\textgreater