Ustilaginoidin D induces hepatotoxicity and behaviour aberrations in zebrafish larvae

Ustilaginoidins, a group of bis-naphtho-γ-pyrones, are one of the major mycotoxins produced by Ustilaginoidea virens. This group of bis-naphtho-γ-pyrone mycotoxins has been demonstrated to have antibacterial and immunological inhibitory activities and strong cytotoxicity to human oral epidermoid carcinoma. However, little is yet known about the toxicity of ustilaginoidins to animals or toxicity mechanisms. In this study, toxicity assays to zebrafish larvae show that ustilaginoidin D is highly toxic to zebrafish with an LC₅₀ of ∼7.50 μM. Ustilaginoidin D causes an obvious yolk sac absorption delay and liver damage in zebrafish, which is indicated by liver atrophy and the increased alanine and aspartate transaminase activities. Interestingly, different doses of ustilaginoidin D can alter zebrafish movement behavior in a distinct manner. Transcriptome analyses show that global gene expression profiling in zebrafish is significantly changed in response to ustilaginoidin D exposure. KEGG pathway analyses reveal that differentially expressed genes are enriched in the pathways related to lipid metabolism and hyperbilirubinemia, which are indicators of severe liver injury. Consistently, the expression of the marker genes for hepatotoxic responses is significantly induced by ustilaginoidin D. The findings indicate that ustilaginoidin D induces lipid metabolism disorders and hepatotoxicity in zebrafish larvae and poses a potential risk to food safety.