Zearalenone, a mycotoxin produced by fungi of the genus Fusarium, widely exists in animal feed and human food. The structure of zearalenone is similar to estrogen, so it mainly has estrogenic effects on various organisms. Products contaminated with zearalenone can pose risks to animals and humans. Therefore, it is imperative to carry out toxicological research on zearalenone and evaluate its risk to human health. This paper briefly introduces the production, physical, and chemical properties of zearalenone and the research progress of its toxicity kinetics, focusing on its genetic toxicity, reproductive toxicity, hepatotoxicity, immunotoxicity, carcinogenicity, endocrine interference, and its impact on intestinal health. Finally, the progress of the risk assessment of human exposure is summarized to provide a reference for the follow-up study of zearalenone.

Zearalenone (ZEA), produced by Fusarium, is a fungal toxin commonly found in maize, wheat, and other cereals. ZEA has the ability to bind to estrogen receptors of humans and animals and is an environmental endocrine disruptor that may interfere with glucose homeostasis and lipid metabolism. In this study, we first investigated the effects of chronic exposure to low doses of ZEA with a high-fat-diet (HFD) in obese C57BL/6 J mice. In the absence of significant toxicity and without affecting glucose tolerance, 50 and 100 μg/kg b. w. ZEA was found to significantly exacerbate lipid synthesis, accumulation and alter the overall transcriptional profile of the liver in mice synergistically with HFD. Validation in combination with AML-12 cells revealed that ZEA promoted lipid synthesis and increased hepatic lipid droplet accumulation via the HNF1β/PPARγ and SREBP1c-HSD17B13/PLINs signal pathways. Further, by analyzing the changes in the intestinal flora of mice and their relationship with lipid metabolism genes, it was found that ZEA decreased the relative abundance of Lactobacillus and increased the relative abundance of Ileococcus, E. faecalis, and Ricardia. These changes were significantly correlated with the expression of Pparg and Srebf1, etc. ZEA may contribute to the abnormality of lipid metabolism by influencing the intestinal microbiota. This study highlights the synergistic effects of long-term low-dose ZEA and excess lipids, providing a theoretical basis for elucidating the mechanism of chronic toxicity of ZEA and its negative impact on metabolic diseases.

Small membranes known as exosomes surround them and are released by several cell types both in vitro and in vivo. These membranes are packed with a variety of biomolecules, including proteins, lipids, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and non-coding RNA (ncRNA). As a source of biological nanomaterials, exosomes play a role in information and substance transmission between cells and have been identified as a general method of facilitating communication during interactions between the body, target organs, and toxins.. In order to understand the changes and mechanism of the composition and level of exosomes after biotoxin infection, this review focuses on current findings on the exosomes and highlights their novel uses in the toxicity mechanism. Exosomes are mainly used as a delivery carrier or mediated by receptors, and play an immune role after the toxin enters the body. This review expounds on the importance of exosomes in the toxicological mechanism of biotoxins and provides new insights for further diagnosis of toxic biomarkers, detoxification, and treatment development. Graphical abstract

Background/Objectives: Metabolic dysfunction-associated steatohepatitis (MASLD) represents a prevalent liver disease worldwide. It is crucial to maintain the stability of the gut–liver axis in order to inhibit the advancement of MASLD. Broccoli-derived exosome-like nanoparticles (BDENs) can alleviate constipation and improve colitis. This study investigated whether BDENs possess therapeutic potential for improving induced MASLD by the gut–liver axis. Methods: BDENs were fractionated from fresh broccoli using differential centrifugation, and the microRNAs were identified and analyzed. 24 male C57BL/6J mice (6 weeks old) were randomized into the control group, HFD group, and BDENs group, with 8 mice per group. After 8 weeks of high-fat diet modeling, the BDENs group accepted BDENs daily oral gavage of 100 mg/kg (B.W.), while the control and HFD groups accepted 1 × PBS. Four weeks after BDENs intervention, analysis was conducted on liver injury markers, liver tissue pathology, intestinal barrier, cecal content metabolomics and fecal 16S rRNA, serum inflammatory factors, and hepatic inflammation. Results: BDENs identified 1659 miRNAs associated with physiological processes such as immunity, antioxidant defense, and fatty acid biosynthesis. BDENs significantly reduced weight and ALT/AST ratio (p < 0.05). Furthermore, BDENs attenuated hepatic histopathological damage and lipid accumulation. For the gut–liver axis, BDENs maintained intestinal barrier, regulated intestinal bile acid metabolism and restored the gut microbiota. Additionally, BDENs reduced serum LPS level (p < 0.01) and suppressed hepatic inflammation, including F4/80 and IL-6, IL-1β (p < 0.0001). Conclusions: Oral BDENs therapy demonstrates potential for ameliorating MASLD.