Ochratoxin C induces zebrafish embryonic neurodevelopmental defects and cerebral hemorrhaging by downregulating Notch...

Ochratoxin C (OTC) is a commonly overlooked toxin in the ochratoxin family, found in moldy crops and poultry meat. However, its potential toxicity should not be ignored and needs further elucidation. In this study, we evaluated the neurotoxicity of OTC during zebrafish embryonic development. The results show that OTC affects the overall zebrafish embryonic development, resulting in reduced body length, abnormal hatching, increased yolk sac area, and decreased tail flick frequency. Additionally, OTC specifically induces cerebral hemorrhaging and abnormal motor behavior in these embryos, accompanied by changes in neurotransmitter and neurodevelopment-related gene expression levels. Furthermore, OTC induces upregulation of oxidative stress levels and downregulation of acetylcholinesterase (AChE) activity and adenosine triphosphatase (ATPase) activity, leading to cell apoptosis.Transcriptional assays and transgenic fluorescence photography show that OTC can inhibit Notch signaling pathway. Partial restoration of cerebral hemorrhage and neurodevelopmental defects can be achieved by administering the Notch signaling activator, sodium propionate. Molecular docking analysis indicates that the gene SLC22A6 (corresponding to the human gene OAT1) as the binding target protein for OTC. In conclusion, OTC exposure may lead to zebrafish embryonic neurodevelopmental defects and cerebral hemorrhage by downregulating Notch signaling. This work provides insight into the potential threat of OTC to embryonic development.