Thesis
Commonly used anti-epileptic drugs are not substrates for the canine and feline ABCG2 transporter
Washington State University
Master of Science (MS), Washington State University
2018
Handle:
https://hdl.handle.net/2376/101169
Abstract
Epilepsy is a chronic condition of recurring unprovoked epileptic seizures. Of the population of idiopathic epileptics, a subset of them fail to respond to medical management. This study investigated whether or not anti-epileptic drugs (AED) are substrates for canine or feline orthologs of the drug efflux transporter ABCG2. Human embryonic kidney cells (HEK-293) that had been stably transfected with plasmids containing either canine or feline ABCG2 cDNA were utilized for these experiments. Levetiracetam, phenobarbital, gabapentin, zonisamide, and lamotrigine were the AED evaluated with a flow cytometry-based competitive transport assay. Intraceullular mitoxantrone, a classic fluorescent ABCG2 substrate. Transfected HEK-293 cells expressing ABCG2 are expected to extrude mitoxantrone from the cell resulting in low intracellular fluorescence. Addition of another ABCG2 substrate results in competition for ABCG2 transport, decreasing mitoxantrone extrusion and increasing intracellular fluorescence. Analysis was performed separately for each AED with either canine or feline ABCG2-transfected cells. One-way ANOVA was used to assess a statistical difference between groups followed by Dunnett's test if a difference was detected. Statistical significance was achieved for one concentration in the canine zonisamide group. Because fluorescence actually decreased, indicating influx rather than efflux, the clinical significance is unknown. Results of this study suggest that ABCG2 does not contribute to pharmacoresistant epilepsy for the evaluated AED.
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Details
- Title
- Commonly used anti-epileptic drugs are not substrates for the canine and feline ABCG2 transporter
- Creators
- Tom Jukier
- Contributors
- Katrina L. Mealey (Degree Supervisor)
- Awarding Institution
- Washington State University
- Academic Unit
- Veterinary Medicine, College of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University; [Pullman, Washington] :
- Identifiers
- 99900525165501842
- Language
- English
- Resource Type
- Thesis