Inhibition of the electron transport chain in propofol induced neurotoxicity in zebrafish embryos.

Lin He, Xuan Wang, Shan Zheng

Neurotoxicology and teratology 2020 Mar - Apr

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Fetal and neonatal exposure to propofol can lead to neuronal death and long-term neurobehavioral deficiencies in both rodents and nonhuman primates. Zebrafish embryo, which is fertilized ex-utero, has provided us a new model species to study the effects of general anesthetics on developing brain. Inhibited electron transport chain leads to mitochondrial dysfunction and insufficient energy production. The aim of this study was to dissect the role of electron transport chain in propofol-induced neurotoxicity. 6 h post fertilization (hpf) zebrafish embryos were exposed to control or 1, 2 or 4 μg/ml propofol until 48hpf. Acridine orange staining was used to assess cell apoptosis in the brain of zebrafish embryos. The activity of mitochondrial electron transport chain complex was assessed using colorimetric method. Expression of key subunit of cytochrome c oxidase was assessed by western blot and transcription level of cox4i1 was assessed by quantitative real time-PCR. The mitochondrial membrane potential and ATP content were assessed. Exposure to 1, 2 and 4 μg/ml propofol induced significant increases in cell apoptosis in the brain of zebrafish embryos in a dose-dependent manner and led to significant decreases in electron transport chain complex IV activity from (0.161 ± 0.023)μmol/mg/min in blank control-treated group to (0.096 ± 0.015)μmol/mg/min, (0.083 ± 0.013)μmol/mg/min and (0.045 ± 0.014)μmol/mg/min respectively, accompanied by decreased expression of key regulatory subunit of cytochrome c oxidase-subunit IV and decreased transcription level of cox4i1. Propofol exposure also decreased the mitochondrial membrane potential and ATP content. Our findings demonstrate that inhibition of the electron transport chain is involved in the mechanisms by which propofol induces neurotoxicity in the developing brain. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Lin He, Xuan Wang, Shan Zheng. Inhibition of the electron transport chain in propofol induced neurotoxicity in zebrafish embryos. Neurotoxicology and teratology. 2020 Mar - Apr;78:106856