Olaquindox (OLA) has been widely used as an animal feed additive in China for decades; however, its toxicity and toxic mechanisms have not been well investigated. In this study, the developmental neurotoxicity and toxic mechanisms of OLA were evaluated in zebrafish. Zebrafish embryos were exposed to different concentrations of OLA (25-1,000 mg/L) from 6 to 120 hours post fertilization (hpf). OLA exposure resulted in many abnormal phenotypes in zebrafish, including shortened body length, notochord degeneration, spinal curvature, brain apoptosis, damage of axon and peripheral motor neuron, and hepatotoxicity. Interestingly, OLA increased zebrafish spontaneous tail coiling, while reduced locomotor capacity. Quantitative polymerase chain reaction (Q-PCR) showed that the expression levels of nine marker genes for nervous system functions or development, namely, α1-tubulin, glial fibrillary acidic protein (gfap), myelin basic protein (mbp), synapsinII a (syn2a), sonic hedgehog a (shha), encoding HuC (elavl3), mesencephalic astrocyte-derived neurotrophic factor (manf) growth associated protein 43 (gap43), and acetylcholinesterase (ache) were all down-regulated significantly in zebrafish after treated with OLA. Besides, the anti-apoptotic and pro-apoptotic genes bcl-2/bax ratio was reduced. These results show that OLA exposure could cause severe developmental neurotoxicity in the early stages of zebrafish life and OLA might induce neurotoxicity by inhibiting the expression of neuro-developmental genes and promoting apoptosis.
Keywords: OLA; developmental neurotoxicity; olaquindox; zebrafish.
© 2020 John Wiley & Sons, Ltd.