ArticleEpilepsia2018
Hepatic and hippocampal cytochrome P450 enzyme overexpression during spontaneous recurrent seizures.
Article in Epilepsia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Microglia Mediate Metabolic Dysfunction From Common Air Pollutants Through NF-κB Signaling.Diabetes · 2024Pooled it
- Comorbidities in the mouse model of temporal lobe epilepsy induced by intrahippocampal kainate.Epilepsia · 2025Article
- Random walk with restart on multilayer networks: from node prioritisation to supervised link prediction and beyond.BMC bioinformatics · 2024Article
- Robust chronic convulsive seizures, high frequency oscillations, and human seizure onset patterns in an intrahippocampal kainic acid model in mice.Neurobiology of disease · 2022Article
- Molecular mechanisms of sex differences in epilepsy and seizure susceptibility in chemical, genetic and acquired epileptogenesis.Neuroscience letters · 2021Review
- Alterations of Cytochrome P450s and UDP-Glucuronosyltransferases in Brain Under Diseases and Their Clinical Significances.Frontiers in pharmacology · 2021Review
- The constitutive androstane receptor and pregnane X receptor in the brain.British journal of pharmacology · 2020Review
- Insights about multi-targeting and synergistic neuromodulators in Ayurvedic herbs against epilepsy: integrated computational studies on drug-target and protein-protein interaction networks.Scientific reports · 2019Article
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Authors and funding
12 authors.
Funding
Abstract
objectiveAvailable evidence points to a role of cytochrome P450 (Cyp) drug biotransformation enzymes in central nervous system diseases, including epilepsy. Deviations in drug pharmacokinetic profiles may impact therapeutic outcomes. Here, we ask whether spontaneous recurrent seizure (SRS) activity is sufficient to modulate the expression of major Cyp enzymes in the liver and brain.
methodsUnilateral intrahippocampal (IH) kainic acid (KA) injections were used to elicit nonconvulsive status epilepticus (SE), epileptogenesis, and SRS, as monitored by video-electroencephalography. Intraperitoneal (IP) KA injection was used to trigger generalized tonic-clonic SE. KA-injected mice and sham controls were sacrificed at 24-72 hours and 1 week post-SE (IH or IP KA), and during the chronic stage (SRS; 6 weeks post-IH KA). Liver and brain tissues were processed for histology, real-time quantitative polymerase chain reaction, Western blot, or microsomal enzymatic assay. Cyp2e1, Cyp3a13, glial fibrillary acidic protein (GFAP), IBA1, xenobiotic nuclear receptors nr1i2 (PXR), nr1i3 (CAR) and nr3c1 (glucocorticoid receptor [GR]) expression was examined. Serum samples were obtained to assay corticosterone levels, a GR activator.
resultsA significant increase of Cyp3a13 and Cyp2e1 transcript level and protein expression was found in the liver and hippocampi during SRS, as compared to control mice. In the ipsilateral hippocampus, Cyp2e1 and Cyp3a protein upregulation during SRS positively correlated to GFAP expression. GFAP SIGNIFICANCE: SRS modifies Cyp expression in the liver and the hippocampus. Nuclear receptors or inflammatory pathways are candidate mechanisms of Cyp regulation during seizures.
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