PUBLICATION
Teratogenic and anticonvulsant effects of zinc and copper valproate complexes in zebrafish
- Authors
- Grünspan, L.D., Mussulini, B.H.M., Baggio, S., Dos Santos, P.R., Dumas, F., Rico, E.P., de Oliveira, D.L., Moura, S.
- ID
- ZDB-PUB-180127-2
- Date
- 2018
- Source
- Epilepsy Research 139: 171-179 (Journal)
- Registered Authors
- Keywords
- Anticonvulsant, Pentylenetetrazole, Teratogenic, Valproate complex, Zebrafish
- MeSH Terms
-
- Animals
- Anticonvulsants/chemistry
- Anticonvulsants/pharmacology*
- Anticonvulsants/toxicity
- Copper/chemistry
- Copper/pharmacology*
- Copper/toxicity
- Dose-Response Relationship, Drug
- Drug Evaluation, Preclinical
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/pathology
- Epilepsy/drug therapy
- Organometallic Compounds/chemistry
- Organometallic Compounds/pharmacology
- Organometallic Compounds/toxicity
- Pentylenetetrazole
- Preliminary Data
- Seizures/drug therapy
- Teratogens/chemistry
- Teratogens/pharmacology*
- Teratogens/toxicity
- Valproic Acid/chemistry
- Valproic Acid/pharmacology*
- Valproic Acid/toxicity
- Zebrafish
- Zinc Compounds/chemistry
- Zinc Compounds/pharmacology*
- Zinc Compounds/toxicity
- PubMed
- 29371041 Full text @ Epilepsy Res.
Citation
Grünspan, L.D., Mussulini, B.H.M., Baggio, S., Dos Santos, P.R., Dumas, F., Rico, E.P., de Oliveira, D.L., Moura, S. (2018) Teratogenic and anticonvulsant effects of zinc and copper valproate complexes in zebrafish. Epilepsy Research. 139:171-179.
Abstract
Valproic acid (VPA) is an antiepileptic drug (AED) that has the broadest spectrum across all types of seizures and epileptic syndromes. Unfortunately, approximately 30% of epileptic patients are refractory to the classical AED. Metal ions have been frequently incorporated into pharmaceuticals for therapeutic or diagnostic purposes and research. In this preliminary study, we assess the embryo toxicity and the anticonvulsant activity of 4 novel metallodrugs, with Zn+2 and Cu+2, a derivative of valproic acid and the N-donor ligand in an adult zebrafish epileptic seizure model induced by pentylenetetrazole. The most toxic complex was [Cu(Valp)2Bipy], in which the LC50 was 0.22 μM at 48 h post fertilization (HPF) and 0.12 μM at 96 HPF, followed by [Zn(Valp)2Bipy] (LC50 = 10 μM). These same metallodrugs ([Cu(Valp)2Bipy] 10 mM/kg and [Zn(Valp)2Bipy] 30 mM and 100 mM/kg) displayed superior activity, thus reducing the seizure intensity by approximately 20 times compared to sodium valproate (175 mM/kg). Overall, [Cu(Valp)2Bipy] showed the best anticonvulsant effects. However, because of the toxicity of copper, [Zn(Valp)2Bipy] is considered the most promising anticonvulsant for future studies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping