Fungi of the different genera produce toxic secondary metabolites. To induce adverse effects in the brain after consumption of contaminated food, these mycotoxins would require to penetrate or weaken the blood-brain barrier. Although neurotoxic effects have been described, a systematic study investigating the effects of mycotoxins on the blood-brain barrier is still missing. In the present study results of an in vitro cell culture model are presented. Primary porcine brain capillary endothelial cells (PBCEC) form a monolayer with strong intercellular tight junctions, which inhibit the paracellular diffusion of xenobiotics into the brain tissue. Before applying the test compounds in transport studies, they were tested for their effects on cellular viability. The integrity of the barrier in vitro was ensured by transendothelial electrical resistances (TEER) of &gt;600 Ω×cm2 analyzed by cellular impedance spectroscopy. The obtained values are much higher and closer to the barrier integrity in vivo compared to commercial brain capillary endothelial cell lines. To determine the rate of blood-brain barrier permeation, samples from the blood and the brain compartment were analyzed at time points up to 48 h via LC-MS/MS and LC-HRMS. Fumonisins (FB1, HFB1), moniliformin (MON), trichothecenes (DON, 3-AcDON), zearalenon (ZEN), α-zearalenol (α-ZEL), ochratoxin A (OTA), ochratoxin α (OTα), citrinin (CIT) and dihydrocitrinone (DHCIT) were chosen as test compounds to cover a wide range of polarity and molecular size. The data show that DON, 3-AcDON, FB1 and OTA disturb the blood-brain barrier integrity by affecting cellular viability and TEER. Furthermore, phase I and II metabolites of ZEN and α-ZEL were detected and quantified. HFB1, ZEN metabolites, OTA, OTα, CIT and DHCIT might be substrates of efflux transporters at the blood-brain barrier.

Mycotoxins at the blood-brain barrier: Metabolism, toxicity, barrier integrity and transfer to the brain

251st National Meeting (2016)

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