Efflux at the Blood-Brain Barrier Reduces the Cerebral Exposure to Ochratoxin A, Ochratoxin α, Citrinin and Dihydrocitrinone

Abstract

Recent studies have implied that environmental toxins, such as mycotoxins, are risk factors for neurodegenerative diseases. To act directly as neurotoxins, mycotoxins need to penetrate or affect the integrity of the blood-brain barrier, which protects the mammalian brain from potentially harmful substances. As common food and feed contaminants of fungal origin, the interest in the potential neurotoxicity of ochratoxin A, citrinin and their metabolites has recently increased. Primary porcine brain capillary endothelial cells were used to investigate cytotoxic or barrier-weakening effects of ochratoxin A, ochratoxin α, citrinin and dihydrocitrinone. The transfer and transport properties of the mycotoxins across the barrier formed by porcine brain capillary endothelial cell monolayers were analysed using HPLC-MS/MS. High levels of Ochratoxin A caused cytotoxic and barrier-weakening effects, whereas ochratoxin α, citrinin and dihydrocitrinone showed no adverse effects up to 10 µM. Likely due to efflux transporter proteins, the transfer to the brain compartment was much slower than expected from their high lipophilicity. Due to their slow transfer across the blood-brain barrier, cerebral exposure of ochratoxin A, ochratoxin α, citrinin and dihydrocitrinone is low and neurotoxicity is likely to play a subordinate role in their toxicity at common physiological concentrations.

Does Digestate Dose Affect Fodder Security and Nutritive Value?

“…These health concerns in humans as well as animals widely affect animal production in the Czech Republic. It is important to note that, apart from the refusal of contaminated feed by animals, a non-negligible increase in expenses on veterinary treatments occurs as well, due to acute and chronic toxicosis [16,24,[35][36][37][38]. This shows a high need for field studies focused on mycotoxins in fodder.…”

Food Toxicity of Mycotoxin Citrinin and Molecular Mechanisms of Its Potential Toxicity Effects through the Implicated Targets Predicted by Computer-Aided Multidimensional Data Analysis

“…Furthermore, based on the excellent solubility values, we hypothesize that citrinin could be effectively absorbed orally after food consumption in the small intestine. Contrary to our study, some reports have concluded that citrinin crosses the BBB model in vitro faster than other mycotoxins [35,39]. We mined functionally related genes from SwissADME, ProTox-II, and the Comparative Toxicogenomics Database (CTD) and created a network of protein-protein interactions through the GeneMANIA database.…”

Electrospun Nanofibers Modified with Copper Nanoparticles for Simultaneous Extraction and Detection of Three Ochratoxins in Foods

“…3 Especially, the OTC can be easily converted into OTA after intake even at very low concentrations. 4 Considering the hepatorenal toxicity, 5 teratogenic, carcinogenic, 6 genotoxic, 7 and immunosuppressive 8 of OTA, many countries and institutions have established strict statute on the threshold in various foods, 9 but a clear limit of OTB and OTC has not been built up. It is worth noting that the foods are rarely contaminated with a single OT; if only OTA is detected, the total intake of OTs is often underestimated.…”