Insights from zebrafish and mouse models on the activity and safety of ar-turmerone as a potential drug candidate for the treatment of epilepsy
- Authors
- Orellana-Paucar, A.M., Afrikanova, T., Thomas, J., Aibuldinov, Y.K., Dehaen, W., de Witte, P.A., and Esguerra, C.V.
- ID
- ZDB-PUB-140213-21
- Date
- 2013
- Source
- PLoS One 8(12): e81634 (Journal)
- Registered Authors
- Esguerra, Camila V.
- Keywords
- none
- MeSH Terms
-
- Animals
- Anticonvulsants/pharmacokinetics*
- Anticonvulsants/pharmacology
- Behavior, Animal/drug effects
- Blood-Brain Barrier*
- Brain/drug effects*
- Brain/metabolism
- Brain/physiopathology
- Brain-Derived Neurotrophic Factor/genetics
- Brain-Derived Neurotrophic Factor/metabolism
- Disease Models, Animal
- Gene Expression Regulation/drug effects
- Injections, Intraperitoneal
- Ketones/pharmacokinetics*
- Ketones/pharmacology
- Male
- Mice
- Mice, Inbred C57BL
- Motor Activity/drug effects
- Pentylenetetrazole
- Postural Balance/drug effects
- Proto-Oncogene Proteins c-fos/genetics
- Proto-Oncogene Proteins c-fos/metabolism
- Seizures/chemically induced
- Seizures/drug therapy*
- Seizures/metabolism
- Seizures/physiopathology
- Sesquiterpenes/pharmacokinetics*
- Sesquiterpenes/pharmacology
- Zebrafish
- PubMed
- 24349101 Full text @ PLoS One
In a previous study, we uncovered the anticonvulsant properties of turmeric oil and its sesquiterpenoids (ar-turmerone, α-, β-turmerone and α-atlantone) in both zebrafish and mouse models of chemically-induced seizures using pentylenetetrazole (PTZ). In this follow-up study, we aimed at evaluating the anticonvulsant activity of ar-turmerone further. A more in-depth anticonvulsant evaluation of ar-turmerone was therefore carried out in the i.v. PTZ and 6-Hz mouse models. The potential toxic effects of ar-turmerone were evaluated using the beam walking test to assess mouse motor function and balance. In addition, determination of the concentration-time profile of ar-turmerone was carried out for a more extended evaluation of its bioavailability in the mouse brain. Ar-turmerone displayed anticonvulsant properties in both acute seizure models in mice and modulated the expression patterns of two seizure-related genes (c-fos and brain-derived neurotrophic factor [bdnf]) in zebrafish. Importantly, no effects on motor function and balance were observed in mice after treatment with ar-turmerone even after administering a dose 500-fold higher than the effective dose in the 6-Hz model. In addition, quantification of its concentration in mouse brains revealed rapid absorption after i.p. administration, capacity to cross the BBB and long-term brain residence. Hence, our results provide additional information on the anticonvulsant properties of ar-turmerone and support further evaluation towards elucidating its mechanism of action, bioavailability, toxicity and potential clinical application.