PUBLICATION
In vitro effects of antiepileptic drugs on acetylcholinesterase and ectonucleotidase activities in zebrafish (Danio rerio) brain
- Authors
- Siebel, A.M., Rico, E.P., Capiotti, K.M., Piato, A.L., Cusinato, C.T., Franco, T.M., Bogo, M.R., and Bonan, C.D.
- ID
- ZDB-PUB-100408-17
- Date
- 2010
- Source
- Toxicology in vitro : an international journal published in association with BIBRA 24(4): 1279-1284 (Journal)
- Registered Authors
- Bonan, Carla Denise
- Keywords
- Acetylcholinesterase, Antiepileptic drugs, Nucleoside triphosphate diphosphohydrolase, Ecto-52-nucleotidase, Zebrafish
- MeSH Terms
-
- 5'-Nucleotidase/metabolism*
- Acetylcholinesterase/metabolism*
- Amines/toxicity
- Animals
- Anticonvulsants/toxicity*
- Brain/drug effects
- Brain/enzymology*
- Carbamazepine/toxicity
- Cyclohexanecarboxylic Acids/toxicity
- Dose-Response Relationship, Drug
- Phenytoin/toxicity
- Zebrafish/metabolism
- gamma-Aminobutyric Acid/toxicity
- PubMed
- 20362660 Full text @ Toxicol. In Vitro
- CTD
- 20362660
Citation
Siebel, A.M., Rico, E.P., Capiotti, K.M., Piato, A.L., Cusinato, C.T., Franco, T.M., Bogo, M.R., and Bonan, C.D. (2010) In vitro effects of antiepileptic drugs on acetylcholinesterase and ectonucleotidase activities in zebrafish (Danio rerio) brain. Toxicology in vitro : an international journal published in association with BIBRA. 24(4):1279-1284.
Abstract
Carbamazepine (CBZ), phenytoin (PHT), and gabapentine (GBP) are classical antiepileptic drugs (AEDs) that act through a variety of mechanisms. We have tested the in vitro effects of CBZ, PHT, and GBP at different concentrations on ectonucleotidase and acetylcholinesterase activities in zebrafish brain. CBZ inhibited ATP hydrolysis at 1000 muM (32%) whereas acetylcholine hydrolysis decreased at 500 muM (25.2%) and 1000 muM (38.7%). PHT increased AMP hydrolysis both at 500 muM (65%) and 1000 muM (64.8%). GBP did not promote any significant changes on ectonucleotidase and acetylcholinesterase activities. These results have shown that CBZ can reduce NTPDase (nucleoside triphosphate diphosphohydrolase) and PHT enhance ecto 5'-nucleotidase activities. Therefore, it is possible to suggest that the AEDs induced-effects on ectonucleotidases are related to enzyme anchorage form. Our findings have also shown that high CBZ concentrations inhibit acetylcholinesterase activity, which can induce an increase of acetylcholine levels. Taken together, these results showed a complex interaction among AEDs, purinergic, and cholinergic systems, providing a better understanding of the AEDs pharmacodymanics.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping