PUBLICATION
Embryonic stage-dependent teratogenicity of ketamine in zebrafish (Danio rerio)
- Authors
- Felix, L.M., Serafim, C., Valentim, A.M., Antunes, L.M., Campos, S., Matos, M., Coimbra, A.M.
- ID
- ZDB-PUB-160701-3
- Date
- 2016
- Source
- Chemical Research in Toxicology 29(8): 1298-309 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Spectrophotometry, Ultraviolet
- Teratogens/toxicity*
- Zebrafish/embryology*
- Chromatography, High Pressure Liquid
- Animals
- Ketamine/toxicity*
- PubMed
- 27359275 Full text @ Chem. Res. Toxicol.
- CTD
- 27359275
Citation
Felix, L.M., Serafim, C., Valentim, A.M., Antunes, L.M., Campos, S., Matos, M., Coimbra, A.M. (2016) Embryonic stage-dependent teratogenicity of ketamine in zebrafish (Danio rerio). Chemical Research in Toxicology. 29(8):1298-309.
Abstract
Ketamine, a widely used anesthetic, has been shown to have NMDA receptor dependent and independent actions during zebrafish (Danio rerio) embryogenesis. Notwithstanding, the effects of developmental toxicity and the mechanisms of ketamine action on fish embryos are still not well understood and its implications for early vertebrate development remain to be clarified. In this work, zebrafish embryos were exposed to ketamine (0.2, 0.4 and 0.8 mg mL-1) in order to study stage-developmental toxicity of this pharmaceutical. During blastula (2.5 hours post fertilization- hpf), gastrula (5.5 hpf) and segmentation (10.5 hpf), embryos were exposed to the referred ketamine concentrations for a period of 20 min and were allowed to grow until 144 hpf. Both lethal and non-lethal parameters were evaluated. Skeletal development was assessed by alcian blue and calcein staining. Additionally, the expression of the developmental genes sonic hedgehog a (shh a) and noggin 3 (nog3) was evaluated. Similar to our previous work, bone and cartilage malformations were observed after blastula exposure. During gastrula, ketamine exposure induced a concentration-dependent mortality and malformations, such as: lordosis and/or kyphosis and microcephaly, namely at higher concentrations. Contrarily, exposure during segmentation showed the induction of non-specific effects with no mortality rise. The quantitative real-time polymerase chain reaction (qRT-PCR) analysis showed differences on shh a and nog3 expressions comparatively to the control group. Overall, this study shows that the ketamine toxic profile is developmental phase-dependent being blastula the most susceptible phase. The effects observed may result from ketamine interaction with cellular signaling pathways that merit further investigation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping