L-Carnitine rescues ketamine-induced attenuated heart rate and MAPK (ERK) activity in zebrafish embryos

Jyotshnabala Kanungo, Elvis Cuevas, Syed F. Ali, Merle G. Paule

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)205-212
Number of pages8
JournalReproductive Toxicology
Volume33
Issue number2
DOIs
StatePublished - Apr 2012
Externally publishedYes

Keywords

  • Heart rate
  • Ketamine
  • L-Carnitine
  • MAPK/ERK
  • SAPK
  • Zebrafish

ASJC Scopus subject areas

  • Toxicology

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