Developmental Neurotoxicity of Trichlorfon in Zebrafish Larvae.

Trichlorfon is an organophosphorus pesticide widely used in aquaculture and has potential neurotoxicity, but the underlying mechanism remains unclear. In the present study, zebrafish embryos were exposed to trichlorfon at concentrations (0, 0.1, 2 and 5 mg/L) used in aquaculture from 2 to 144 h post fertilization. Trichlorfon exposure reduced the survival rate, hatching rate, heartbeat and body length and increased the malformation rate of zebrafish larvae. The locomotor activity of larvae was significantly reduced. The results of molecular docking revealed that trichlorfon could bind to acetylcholinesterase (AChE). Furthermore, trichlorfon significantly inhibited AChE activity, accompanied by decreased acetylcholine, dopamine and serotonin content in larvae. The transcription patterns of genes related to acetylcholine (e.g., ache, chrna7, chata, hact and vacht), dopamine (e.g., drd4a and drd4b) and serotonin systems (e.g., tph1, tph2, tphr, serta, sertb, htrlaa and htrlab) were consistent with the changes in acetylcholine, dopamine, serotonin content and AChE activity. The genes related to the central nervous system (CNS) (e.g., a1-tubulin, mbp, syn2a, shha and gap-43) were downregulated. Our results indicate that the developmental neurotoxicity of trichlorfon might be attributed to disorders of cholinergic, dopaminergic and serotonergic signaling and the development of the CNS.

Neurotoxicity of an emerging organophosphorus flame retardant, resorcinol bis(diphenyl phosphate), in zebrafish larvae.

Resorcinol bis(diphenyl phosphate) (RDP), an emerging organophosphorus flame retardant and alternative to triphenyl phosphate (TPHP), is a widespread environmental pollutant. The neurotoxicity of RDP has attracted much attention, as RDP exhibits a similar structure to TPHP, a neurotoxin. In this study, the neurotoxicity of RDP was investigated by using a zebrafish (Danio rerio) model. Zebrafish embryos were exposed to RDP (0, 0.3, 3, 90, 300 and 900 nM) from 2 to 144 h postfertilization. After this exposure, the decreased heart rates and body lengths and the increased malformation rates were observed. RDP exposure significantly reduced the locomotor behavior under light-dark transition stimulation and the flash stimulus response of larvae. Molecular docking results showed that RDP could bind to the active site of zebrafish AChE and that RDP and AChE exhibit potent binding affinity. RDP exposure also significantly inhibited AChE activity in larvae. The content of neurotransmitters (γ-aminobutyric, glutamate, acetylcholine, choline and epinephrine) was altered after RDP exposure. Key genes (α1-tubulin, mbp, syn2a, gfap, shhα, manf, neurogenin, gap-43 and ache) as well as proteins (α1-tubulin and syn2a) related to the development of the central nervous system (CNS) were downregulated. Taken together, our results showed that RDP can affect different parameters related to CNS development, eventually leading to neurotoxicity. This study indicated that more attention should be paid to the toxicity and environmental risk of emerging organophosphorus flame retardants.