Transport of enniatin B and enniatin B1 across the blood-brain barrier and hints for neurotoxic effects in cerebral cells

Abstract

Enniatins are common contaminants of food and feed and belong to the group of the “emerging” mycotoxins, which are produced by various Fusarium species. Although a wide range of toxic effects, like antibacterial, antifungal, insecticidal and cytotoxic properties, have been described in vitro, so far, no cases of mycotoxicosis connected to enniatins in vivo are reported. Among this group of mycotoxins, enniatin B and enniatin B1 are the most prevalent compounds and therefore are present in the human diet. Enniatins can reach systemic circulation, thus, the investigation of possible neurotoxic effects is of importance. Different cerebral cells were used to address effects on cell death having an impact on the blood-brain barrier. The influence of enniatin B and enniatin B1 on cellular viability was examined via Cell Counting kit-8 assay (CCK-8) in three different cell types of the blood-brain barrier: porcine brain capillary endothelial cells (PBCEC), human brain microvascular endothelial cells (HBMEC) and human astrocytoma cells (CCF-STTG1). CCF-STTG1 cells were more sensitive to enniatin B (IC50 = 8.9 μM) and enniatin B1 (IC50 = 4.4 μM) than both endothelial cell types. In CCF-STTG1 cells, caspase-3 activation and lactate dehydrogenase (LDH) release were evaluated. Both compounds did not induce any LDH release and only enniatin B increased caspase-3 activity as a marker for apoptosis. The transport kinetics of enniatin B and enniatin B1 across the blood-brain barrier in vitro were evaluated using PBCEC, cultivated on Transwell® filter inserts. Analysis of the apical and the basolateral compartment by high performance liquid chromatography-mass spectrometry revealed high influx rates for enniatin B and enniatin B1. Thus, both compounds can reach the brain parenchyma where neurotoxic effects cannot be ruled out.

Cytoprotective Effects of Fish Protein Hydrolysates against H2O2-Induced Oxidative Stress and Mycotoxins in Caco-2/TC7 Cells

“…They reported an occurrence of ENs in up to 25% of analyzed samples ( n = 20) at levels from 1.01 to 119.0 µg/Kg, and revealed higher average concentrations of EN A1 (11.1 µg/Kg), EN B (13.0 µg/Kg), and EN B1 (19.0 µg/Kg) in head than in liver (5.1, 12.6, and 5.3 µg/Kg for EN A1, EN B, and EN B1, respectively). Those findings corroborate the ability of ENs to distribute and persist into tissues, and even penetrate different barriers, including the blood-brain barrier, in higher organisms as previously evidenced in the literature [ 80 , 81 ]. However, mycotoxins were not detected in the protein hydrolysates, suggesting that the fish had not been exposed to mycotoxins.…”

An Insight into the Roles of Dietary Tryptophan and Its Metabolites in Intestinal Inflammation and Inflammatory Bowel Disease

“…Disruption in the integrity and function of the intestinal epithelial barrier could lead to the enhancement the permeability of the pathogens and toxins, which can enter into the tissues, blood, and lymphatic vessels, and increase the risk of infection in IBD. [ 199 ] It was demonstrated that AhR activation could protect junctional complexes in the intestinal epithelium and mediate cytokine expression. [ 200 ] Likewise, AhR activation in intestinal epithelial cells can protect the stem cell niche and restore the barrier homeostasis, whereas its deficiency promotes inflammation.…”

Comparative Structure–Activity Analysis of the Antimicrobial Activity, Cytotoxicity, and Mechanism of Action of the Fungal Cyclohexadepsipeptides Enniatins and Beauvericin

“…Other foods, like nuts, spices, fruits, and their by-products can also be contaminated by these fungal metabolites [11]. In terms of toxicity, ENN and BEA have been shown to be toxic to different animals and humans cell types causing apoptosis, mitochondrial damages, and reactive oxygen species (ROS) production [7,8,10,14,15].…”