title: Influence of T-2 and HT-2 toxin on the blood-brain barrier in vitro: new experimental hints for neurotoxic effects.
abstract: The trichothecene mycotoxin T-2 toxin is a common contaminant of food and feed and is also present in processed cereal derived products. Cytotoxic effects of T-2 toxin and its main metabolite HT-2 toxin are already well described with apoptosis being a major mechanism of action. However, effects on the central nervous system were until now only reported rarely. In this study we investigated the effects of T-2 and HT-2 toxin on the blood-brain barrier (BBB) in vitro. Besides strong cytotoxic effects on the BBB as determined by the CCK-8 assay, impairment of the barrier function starting at low nanomolar concentrations were observed for T-2 toxin. HT-2 toxin, however, caused barrier disruption at higher concentrations compared to T-2 toxin. Further, the influence on the tight junction protein occludin was studied and permeability of both toxins across the BBB was detected when applied from the apical (blood) or the basolateral (brain) side respectively. These results clearly indicate the ability of both toxins to enter the brain via the BBB.
authors.affiliation: Institute of Food Chemistry, Westfälische Wilhelms-Universität Münster, Münster, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Weidner
authors.forename: Sabine
authors.initials: S
authors.lastname: Hüwel
authors.forename: Franziska
authors.initials: F
authors.lastname: Ebert
authors.forename: Tanja
authors.initials: T
authors.lastname: Schwerdtle
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Galla
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Humpf
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D002196:Capillaries / Q000166:cytology; D016923:Cell Death / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017097:Electric Impedance; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D009498:Neurotoxins / Q000737:chemistry / Q000633:toxicity*; D062793:Occludin / Q000378:metabolism; D013395:Sucrose / Q000378:metabolism; D034421:Sus scrofa; D013605:T-2 Toxin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity*; D013997:Time Factors
chemical_list: D009498:Neurotoxins; D062793:Occludin; D013395:Sucrose; D013605:T-2 Toxin; C012351:HT-2 toxin
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