Apoptotic mechanism of development inhibition in zebrafish induced by esketamine

Yuan, Wenjuan; Xiao, Yinggang; Zhang, Yang; Xiang, Kuilin; Huang, Tianfeng; Diaby, Mohamed; Gao, Ju

doi:10.1016/j.taap.2023.116789

Cited by 4 publications

(2 citation statements)

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“…But, after exposure to esketamine, we saw a marked increase in larval hatching at 60 hpf. This discovery is consistent with the findings published by Wenjuan Yuan et al [ 16 ]. It is assumed that the increased hatching may be associated with esketamine-induced changes in enzyme activity and abnormal muscle responses [ 24 , 25 ].…”

Section: Discussionsupporting

confidence: 94%

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Esketamine Exposure Impairs Cardiac Development and Function in Zebrafish Larvae

Huang,

Wang,

Lin

et al. 2024

Toxics

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Esketamine is a widely used intravenous general anesthetic. However, its safety, particularly its effects on the heart, is not fully understood. In this study, we investigated the effects of esketamine exposure on zebrafish embryonic heart development. Zebrafish embryos were exposed to esketamine at concentrations of 1, 10, and 100 mg/L from 48 h post-fertilization (hpf) to 72 hpf. We found that after exposure, zebrafish embryos had an increased hatching rate, decreased heart rate, stroke volume, and cardiac output. When we exposed transgenic zebrafish of the Tg(cmlc2:EGFP) strain to esketamine, we observed ventricular dilation and thickening of atrial walls in developing embryos. Additionally, we further discovered the abnormal expression of genes associated with cardiac development, including nkx2.5, gata4, tbx5, and myh6, calcium signaling pathways, namely ryr2a, ryr2b, atp2a2a, atp2a2b, slc8a3, slc8a4a, and cacna1aa, as well as an increase in acetylcholine concentration. In conclusion, our findings suggest that esketamine may impair zebrafish larvae’s cardiac development and function by affecting acetylcholine concentration, resulting in weakened cardiac neural regulation and subsequent effects on cardiac function. The insights garnered from this research advocate for a comprehensive safety assessment of esketamine in clinical applications.

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Section: Discussionsupporting

confidence: 94%

“…Esketamine has an LD50 value of 2471.5 mg/L for zebrafish embryos at 96 hpf, and 548 mg/L is the maximum safe concentration for prolonged exposure to esketamine [ 16 ]. Adult zebrafish exhibit anxiety-like behaviors when exposed to 20 mg/L of ketamine [ 17 ].…”

Section: Introductionmentioning

confidence: 99%