Zearalenone-14-glucoside forms a self-assembled supramolecular gel with enhanced toxicity through cytochrome P450 depletion.

Zearalenone-14-glucoside (Z14G) is a widely contaminating modified mycotoxin in the global food and feed. For the first time, we report that Z14G formed a self-assembled supramolecular gel. Results from our morphological and chemical characterizations, rheological testing, and molecular simulation dynamics demonstrated that Z14G is a type of thermal-responsive, self-assembled supramolecular gel. Both the microbial key metabolic enzymes (MKME)-Caco2/HepG2 and rat metabolic models were adopted to explore the release of Z14G. These in vivo and in vitro results suggested that Z14G slowly released ZEN. Toxicological experiments and proteomics demonstrated that Z14G led to stronger tissue toxicity than ZEN, which was achieved by depleting cytochrome P450. By revealing the self-assembly and self-release, characteristics of natural pollutant Z14G, this study suggests that the self-assembled supramolecular gel of this foodborne pollutant may pose a higher toxicity to human health. Collectively, this work allows for better understanding of natural self-assembly supramolecular gels in the field of toxicology.