Nano-TiO₂ aggravates bioaccumulation and developmental neurotoxicity of triphenyl phosphate in zebrafish larvae

This study explored the combined effects of titanium dioxide nanoparticles (nano-TiO₂) and triphenyl phosphate (TPhP) on the neurodevelopment of zebrafish larvae as well as the underlying mechanisms. With this regard, zebrafish embryos were exposed to nano-TiO₂ of 100 μg·L^-1, TPhP of 0, 8, 24, 72, and 144 μg·L^-1, or their combinations until 120 h post-fertilization (hpf). Results indicated 100 μg·L^-1 nano-TiO₂ alone to be nontoxic to zebrafish larvae. However, obvious developmental toxicity manifested as inhibition of surviving rate, heart rate and body length as well as increased malformation was observed in the higher concentrations of TPhP (72 and 144 μg·L^-1) alone and the co-exposure groups. Additionally, results suggested that nano-TiO₂ significantly enhanced the bioaccumulation of TPhP in zebtafish larvae, and thus aggravated the abnormities of spontaneous movement and swimming behavior in zebrafish larvae induced by TPhP. Nano-TiO₂ also exacerbated the TPhP-induced inhibition of the axonal growth on the secondary motor neuron, and aggravated the TPhP-induced decrease on expressions of neuron-specific green fluorescent protein (GFP) and neuronal marker genes (ngn1 and elavl3). Further, the content of neurotransmitter serotonin was not altered by TPhP alone exposure, but was decreased significantly in the co-exposure group of 144 μg·L^-1 TPhP and nano-TiO₂. Our data indicated that nano-TiO₂ might aggravate the neuron abnormities and serotonin system dysfunction by enhancing the TPhP accumulation, leading to exacerbated abnormal locomotors in zebrafish larvae.