Abstract
Ketamine, an antagonist of the N-methyl-D-aspartate (NMDA)-type glutamate receptors, is a pediatric anesthetic. Ketamine has been shown to be neurotoxic and cardiotoxic in mammals. Here, we show that after 2 h of exposure, 5 mM ketamine significantly reduced heart rate in 26 h old zebrafish embryos. In 52 h old embryos, 1 mM ketamine was effective after 2 h and 0.5 mM ketamine at 20 h of exposure. Ketamine also induced significant reductions in activated MAPK (ERK) levels. Treatment of the embryos with the ERK inhibitor, PD 98059, also significantly reduced heart rate whereas the p38/SAPK inhibitor, SB203580, was ineffective. Ketamine is known to inhibit lipolysis and a decrease of ATP content in the heart. Co-treatment with l-carnitine that enhances fatty acid metabolism effectively rescued ketamine-induced attenuated heart rate and ERK activity. These findings demonstrate that l-carnitine counteracts ketamine's negative effects on heart rate and ERK activity in zebrafish embryos.
Published by Elsevier Inc.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Analgesics / adverse effects
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Animals
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Cardiotonic Agents / pharmacology*
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Carnitine / pharmacology*
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Embryo, Nonmammalian / drug effects
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Embryo, Nonmammalian / physiology
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Excitatory Amino Acid Antagonists / adverse effects
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / physiology*
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Flavonoids / pharmacology
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Heart Rate / drug effects*
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Ketamine / adverse effects
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Protein Kinase Inhibitors / pharmacology
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Vitamin B Complex
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Zebrafish
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / physiology
Substances
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Analgesics
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Cardiotonic Agents
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Excitatory Amino Acid Antagonists
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Flavonoids
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Protein Kinase Inhibitors
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Receptors, N-Methyl-D-Aspartate
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Vitamin B Complex
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Ketamine
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Extracellular Signal-Regulated MAP Kinases
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p38 Mitogen-Activated Protein Kinases
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Carnitine
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one