Developmental Neurotoxicity of Anesthetic Etomidate on Zebrafish Larvae.

Etomidate (ET) is widely used as an anesthetic in clinical practice. The long-term use of ET can lead to negative effects, such as decreased consciousness and cognitive impairment. However, the developmental neurotoxicity of ET on fish remains unclear. To address this issue, zebrafish embryos were exposed to ET from 2 hpf (hours post-fertilization) to 168 hpf at 0. 010, 0. 091, 0. 501, 9. 400, 84. 31 and 664. 4 μg·L^-1. The physiological development, behavior and cell apoptosis, and transcriptional expression of genes related to dopamine (DA) and γ-aminobutyric acid (GABA) pathway were detected to investigate the developmental neurotoxicity of ET. The results showed that 664.4 μg·L^-1 ET decreased hatching rate at 48 hpf and 60 hpf. 0.091 μg·L^-1 and 0.501 μg· L^-1 ET decreased body length in larvae at 168 hpf. At 48 hpf, 0.010, 0.091, 0.501, 9.400, 84.31 and 664.4 μg·L^-1 ET increased malformation. 0.501, 9.400, 84.31 and 664.4 μg·L^-1 ET increased malformation at 96 hpf. Additionally, 0.501, 9.400 and 664.4 μg·L^-1 ET increased malformation at 168 hpf. The 0.010 μg·L^-1 ET caused cell apoptosis in the brain, while 664.4 μg·L^-1 ET inhibited apoptosis. In addition, behavior analysis indicated that ET inhibited touch behavior at all concentrations. The 0.091 μg·L^-1 ET enhanced swimming behavior in zebrafish larvae, while 664.4 μg·L^-1 ET weakened swimming behavior. ET increased anxious behavior in a concentration-dependent manner. The qPCR data showed that ET up-regulated the transcriptions of genes related to DA and GABA pathway at low concentration, while ET down-regulated the transcriptions of these genes at high concentration. The above results indicate that ET has significant neurodevelopmental toxicity in early development of zebrafish. [ABSTRACT FROM AUTHOR]