PUBLICATION
N-acetylcysteine prevents ketamine-induced adverse effects on development, heart rate and monoaminergic neurons in zebrafish
- Authors
- Robinson, B., Dumas, M., Gu, Q., Kanungo, J.
- ID
- ZDB-PUB-180612-6
- Date
- 2018
- Source
- Neuroscience letters 682: 56-61 (Journal)
- Registered Authors
- Keywords
- 5-HT, Developmental toxicity, Ketamine, N-acetyl cysteine, Tyrosine hydroxylase, Zebrafish
- MeSH Terms
-
- Acetylcysteine/pharmacology*
- Anesthetics, Dissociative/toxicity
- Animals
- Biogenic Monoamines/antagonists & inhibitors*
- Biogenic Monoamines/physiology
- Dose-Response Relationship, Drug
- Embryo, Nonmammalian/drug effects*
- Embryo, Nonmammalian/physiology
- Embryonic Development/drug effects
- Embryonic Development/physiology
- Free Radical Scavengers/pharmacology
- Heart Rate/drug effects*
- Heart Rate/physiology
- Ketamine/toxicity*
- Neurons/drug effects*
- Neurons/physiology
- Zebrafish
- PubMed
- 29890257 Full text @ Neurosci. Lett.
Citation
Robinson, B., Dumas, M., Gu, Q., Kanungo, J. (2018) N-acetylcysteine prevents ketamine-induced adverse effects on development, heart rate and monoaminergic neurons in zebrafish. Neuroscience letters. 682:56-61.
Abstract
N-acetylcysteine, a precursor molecule of glutathione, is an antioxidant. Ketamine, a pediatric anesthetic, has been implicated in cardiotoxicity and neurotoxicity including modulation of monoaminergic systems in mammals and zebrafish. Here, we show that N-acetylcysteine prevents ketamine's adverse effects on development and monoaminergic neurons in zebrafish embryos. The effects of ketamine and N-acetylcysteine alone or in combination were measured on the heart rate, body length, brain serotonergic neurons and tyrosine hydroxylase-immunoreactive (TH-IR) neurons. In the absence of N-acetylcysteine, a concentration of ketamine that produces an internal embryo exposure level comparable to human anesthetic plasma concentrations significantly reduced heart rate and body length and those effects were prevented by N-acetylcysteine co-treatment. Ketamine also reduced the areas occupied by serotonergic neurons in the brain, whereas N-acetylcysteine co-exposure counteracted this effect. TH-IR neurons in the embryo brain and TH-IR cells in the trunk were significantly reduced with ketamine treatment, but not in the presence of N-acetylcysteine. In our continued search for compounds that can prevent ketamine toxicity, this study using specific endpoints of developmental toxicity, cardiotoxicity and neurotoxicity, demonstrates protective effects of N-acetylcysteine against ketamine's adverse effects. This is the first study that shows the protective effects of N-acetylcysteine on ketamine-induced developmental defects of monoaminergic neurons as observed in a whole organism.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping