Early developmental effects of propofol exposure in different stages of zebrafish embryos.

Abstract

The mechanism of action of propofol, a common intravenous anaesthetic, in early life stages is not well understood with contradictory studies showing neurotoxic and neurogenic effects in the developing brain. Zebrafish early life stages have been established as an alternative model for animal experimentation with propofol toxicological effects reported following chronic exposure. Yet, the acute exposure to other anaesthetics has been shown to induce early life stage-dependent toxicological outcomes. Therefore, the present study aimed to evaluate the teratogenic effects of propofol at the 256-cell, 50 % epiboly and 1-4 somite stages following a 20 min exposure. Embryos were exposed after primarily assessment of propofol acute toxicity (24h-LC₅₀=9.82 μg mL^-1) and absorption at different developmental stages by chromatography. Embryos (2 hours post-fertilization, hpf) were treated with an anaesthetic and toxicological concentration of propofol (2.5 and 10 μg mL^-1, respectively) for 20-min. Mortality and developmental toxicity were then evaluated until 144 hpf, when the behaviour and oxidative-stress-related biomarkers were assessed. Exposure at the 256-cell stage resulted in a concentration-dependent increased number of abnormalities in head, fins and tail and a decreased body length as well as in changes in ATPase activity for the lowest concentration. On the other hand, exposure at later stages resulted in a decreased survival while no significant malformations were detected. Yet, exposure during the 50 % epiboly stage resulted in the increase of ROS levels as well as glutathione (GST and GSSG) levels while exposure at 1-4 somite stage resulted in increased DNA damage and ATPase alterations. The behaviour of zebrafish was similar among treatments. Overall, these findings show highlight the stage-dependent teratogenic potential of short propofol exposures during zebrafish early development. The alterations observed may be linked to the activation of the zygotic transcription in embryos, requiring further studies to delve into the molecular changes underlying the observed effects.