PUBLICATION
Sodium valproate exposure influences the expression of pparg in the zebrafish model
- Authors
- Merola, C., Caioni, G., Cimini, A., Perugini, M., Benedetti, E.
- ID
- ZDB-PUB-230215-37
- Date
- 2023
- Source
- Birth defects research 115(6): 658-667 (Journal)
- Registered Authors
- Keywords
- PPARs, cartilage disruption, in vivo model, morphometric signatures, teratogenic chemicals
- MeSH Terms
-
- Teratogens/metabolism
- Teratogens/toxicity
- Animals
- Zebrafish Proteins
- Valproic Acid*/metabolism
- Valproic Acid*/toxicity
- Zebrafish/metabolism
- PPAR gamma/metabolism
- Teratogenesis*
- PubMed
- 36786327 Full text @ Birth Defects Res
Citation
Merola, C., Caioni, G., Cimini, A., Perugini, M., Benedetti, E. (2023) Sodium valproate exposure influences the expression of pparg in the zebrafish model. Birth defects research. 115(6):658-667.
Abstract
Valproic acid (VPA) is an anti-epileptic drug used alone or in combination with other medications to treat seizures, mania, and bipolar disorder. VPA recognized as a teratogenic chemical can cause severe birth defects mainly affecting the brain and spinal cord when administered during pregnancy. However, the potential mechanisms of developmental toxicity are still less studied, and in the present study, the influence of VPA exposure was evaluated on zebrafish early-life stages. Zebrafish were exposed to two sublethal concentrations of sodium valproate (SV) (0.06 mM and 0.15 mM) from 24 hours post-fertilization (hpf) to 96 hpf and the SV teratogenic potential was investigated through morphometric analysis of zebrafish larvae combined with the evaluation of cartilage profile. Moreover, the effect of SV on the transcription level of pparg was also performed. The results of the study showed the teratogenic potential of SV, which disrupts the morphometric signature of the head and body. The marked distortion of cartilage structures was paralleled to a malformation of telencephalon and optic tectum in both concentrations suggesting a high teratogen effect of SV on the brain. These data were further confirmed by the increased expression of pparg in the zebrafish head. Overall, the present study confirms the teratogenic activity of SV in the zebrafish model and, for the first time, points out the potential protective role of pparg in the SV dose-dependent toxicity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping