In vitro effects of antiepileptic drugs on acetylcholinesterase and ectonucleotidase activities in zebrafish (Danio rerio) brain

In vitro effects of antiepileptic drugs on acetylcholinesterase and ectonucleotidase activities in zebrafish (Danio rerio) brain

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 bra...

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Bibliographic Details
Published in:Toxicology in vitro Vol. 24; no. 4; pp. 1279 - 1284
Main Authors: Siebel, A.M., Rico, E.P., Capiotti, K.M., Piato, A.L., Cusinato, C.T., Franco, T.M.A., Bogo, M.R., Bonan, C.D.
Format: Journal Article
Language:English
Published: England Elsevier Ltd 01-06-2010
Subjects:
5'-Nucleotidase - metabolism
Acetylcholinesterase
Acetylcholinesterase - metabolism
Amines - toxicity
Animals
Anticonvulsants - toxicity
Antiepileptic drugs
Brain - drug effects
Brain - enzymology
Carbamazepine - toxicity
Cyclohexanecarboxylic Acids - toxicity
Danio rerio
Dose-Response Relationship, Drug
Ecto-5′-nucleotidase
Freshwater
gamma-Aminobutyric Acid - toxicity
Nucleoside triphosphate diphosphohydrolase
Phenytoin - toxicity
Zebrafish
Zebrafish - metabolism
AChE
CNS
Zebrafish
Acetylcholinesterase
Ecto-5′-nucleotidase
AEDs
GBP
BuChE
CBZ
Nucleoside triphosphate diphosphohydrolase
NTPDase
PHT
Antiepileptic drugs
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Summary: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 1000μM (32%) whereas acetylcholine hydrolysis decreased at 500μM (25.2%) and 1000μM (38.7%). PHT increased AMP hydrolysis both at 500μM (65%) and 1000μM (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 pharmacodynamics.
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content type line 23
ISSN:0887-2333
1879-3177
DOI:10.1016/j.tiv.2010.03.018