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.

Dietary mycotoxins, co-exposure, and carcinogenesis in humans: Short review

“…The T-2 and HT-2 toxins are produced by various Fusarium species, particularly F. sporotrichioides and F. poae, reportedly affecting several major cereal crops including oats, barley, corn, and wheat (Weidner et al 2013). A European evaluation of consumer goods found oats and oat products contained the highest summed concentrations of these two contaminants (EFSA Panel on Contaminants in the Food Chain 2011).…”

“…Recent research has discovered evidence for these toxins crossing the blood-brain barrier in vitro, linking them to neurotoxic effects (Weidner et al 2013). However, the predominant human health effects reported in literature associate these toxins with inhibited protein synthesis and apoptosis in a wide variety of in vitro and ex vitro cells, as well as in vivo organs, including brain, gastrointestinal tract, skin, spleen, and thymus (Li et al 2011; EFSA Panel on Contaminants in the Food Chain 2011).…”

Elimination of damaged mitochondria through mitophagy reduces mitochondrial oxidative stress and increases tolerance to trichothecenes

“…Controlling their accumulation in small grains remains a huge challenge. Trichothecenes cause growth retardation, hemorrhagic lesions, immune dysfunction, and emesis (2,3) and are neurotoxic (4)(5)(6). Trichothecene poisoning causes acute gastroenteritis and has been linked to alimentary toxic aleukia (ATA) and Kashin-Beck disease, an endemic and chronic degenerative osteoarthritis (3).…”

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

“…Dermal and subcutaneous exposure to these trichothecenes leads to increased production of ROS, protein carbonyls, lipid peroxidation, and depletion of reduced glutathione [290]. This class of mycotoxin is also known to induce increased permeability, or even frank disruption, of the bloodbrain barrier in animal subjects even at nanomolar concentrations [291,292]. Macrocyclic trichothecenes, such as those produced by SC [293], can also activate p38, JNK, ERK, and MAPK kinases simultaneously, once again via the induction of ribotoxic stress [239,294].…”