ArticleJournal of molecular neuroscience : MN2022
The Prevention and Reversal of a Phenytoin-Resistant Model by N-acetylcysteine Therapy Involves the Nrf2/P-Glycoprotein Pathway at the Blood-Brain Barrier.
Article in Journal of molecular neuroscience : MN, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 4 citations in OpenAlex.
- Audiogenic Kindling Stimulation Fails to Induce Cerebral Overexpression of P-Glycoprotein and Limbic Crises in the GASH/Sal Model of Epilepsy.International journal of molecular sciences · 2026Article
- Drug-resistant Epilepsy: Which Drugs are Substrates of P-glycoprotein and Which are Not?Current neuropharmacology · 2026Review
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
- GLS2 reduces the occurrence of epilepsy by affecting mitophagy function in mouse hippocampal neurons.CNS neuroscience & therapeutics · 2024Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The transporter hypothesis is one of the most popular hypotheses of drug-resistant epilepsy (DRE). P-glycoprotein (P-gp), a channel protein at the blood-brain barrier (BBB), plays an important role in the transport of some anti-seizure drugs from brain tissue into vessels, which reduces drug concentrations and diminishes the effects of drug treatment. We performed this study to test whether P-gp is overexpressed in DRE and identify ways to prevent and reverse DRE. In this study, we established a phenytoin (PHT)-resistant mouse model and revealed that P-gp was overexpressed at the BBB in PHT-resistant mice. The P-gp inhibitor nimodipine decreased the resistance of phenytoin. Antioxidative preventive treatment with N-acetylcysteine (NAC) prevented the mice from entering a PHT-resistant state, and NAC therapy tended to reverse PHT resistance into sensitivity. We were also able to induce PHT resistance by activating the Nrf2/P-gp pathway, which indicates that oxidative stress plays an important role in drug resistance. Taken together, these findings suggest that antioxidative therapy may be a promising strategy for overcoming DRE.
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Registered trials
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