ArticleJournal of applied toxicology : JAT2014
Ketamine attenuates cytochrome p450 aromatase gene expression and estradiol-17β levels in zebrafish early life stages.
Article in Journal of applied toxicology : JAT, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 33 citations in OpenAlex.
- Dose and duration dependent effects of borax on ovarian structure and function in female rats.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Article
- Nifedipine toxicity is exacerbated by acetyl l-carnitine but alleviated by low-dose ketamine in zebrafish in vivo.Journal of applied toxicology : JAT · 2020Article
- Ketamine-induced attenuation of reactive oxygen species in zebrafish is prevented by acetyl l-carnitine in vivo.Neuroscience letters · 2019Article
- N-acetylcysteine prevents ketamine-induced adverse effects on development, heart rate and monoaminergic neurons in zebrafish.Neuroscience letters · 2018Article
- Cyclosporine exacerbates ketamine toxicity in zebrafish: Mechanistic studies on drug-drug interaction.Journal of applied toxicology : JAT · 2017Article
- Acetyl L-carnitine targets adenosine triphosphate synthase in protecting zebrafish embryos from toxicities induced by verapamil and ketamine: An in vivo assessment.Journal of applied toxicology : JAT · 2017Article
- Selective regulation of neurosteroid biosynthesis under ketamine-induced apoptosis of cortical neurons in vitro.Molecular medicine reports · 2016Article
- Opposing effects of ketamine and acetyl L-carnitine on the serotonergic system of zebrafish.Neuroscience letters · 2015Article
- Developmental toxicity assay using high content screening of zebrafish embryos.Journal of applied toxicology : JAT · 2015Article
- Structural analysis of metabolites of asiatic acid and its analogue madecassic acid in zebrafish using LC/IT-MSn.Molecules (Basel, Switzerland) · 2015Article
- Distinct effects of ketamine and acetyl L-carnitine on the dopamine system in zebrafish.Neurotoxicology and teratologyArticle
- Mechanistic studies on ketamine-induced mitochondrial toxicity in zebrafish embryos.Neurotoxicology and teratologyArticle
- Acetyl L-carnitine protects motor neurons and Rohon-Beard sensory neurons against ketamine-induced neurotoxicity in zebrafish embryos.Neurotoxicology and teratologyArticle
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Ketamine, a dissociative anesthetic, is a noncompetitive antagonist of N-methyl-D-aspartate-type glutamate receptors. In rodents and non-human primates as well as in zebrafish embryos, ketamine has been shown to be neurotoxic. In cyclic female rats, ketamine has been shown to decrease serum estradiol-17β (E2) levels. E2 plays critical roles in neurodevelopment and neuroprotection. Cytochrome p450 (CYP) aromatase catalyzes E2 synthesis from androgens. Although ketamine down-regulates a number of CYP enzymes in rodents, its effect on the CYP aromatase (CYP19) is not known. Zebrafish have been used as a model system for examining mechanisms underlying drug effects. Here, using wild-type (WT) zebrafish (Danio rerio) embryos, we demonstrate that ketamine significantly reduced E2 levels compared with the control. However, the testosterone level was elevated in ketamine-treated embryos. These results are concordant with data from mammalian studies. Ketamine also attenuated the expression of the ovary form of CYP aromatase (cyp19a1a) at the transcriptional level but not the brain form of aromatase, cyp19a1b. Exogenous E2 potently induced the expression of cyp19a1b and vtg 1, both validated biomarkers of estrogenicity and endocrine disruption, but not cyp19a1a expression. Attenuation of activated ERK/MAPK levels, reportedly responsible for reduced human cyp19 transcription, was also observed in ketamine-treated embryos. These results suggest that reduced E2 levels in ketamine-treated embryos may have resulted from the suppression of cyp19a1a transcription.
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