2023/04/17 by Sahar A. Harby, Nehal Adel Khalil, Nehal A. Khalil +5
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Genetics and Neurodevelopmental Disorders #Neuroscience and Neuropharmacology Research #Protein Kinase Regulation and GTPase Signaling
paper · pdf · doi:10.1007/s00210-023-02485-7
crossref issued 2023/04/17 · crossref published 2023/04/17 · crossref published-online 2023/04/17 · openalex publication_date 2023/04/17 · crossref created 2023/04/17 · crossref deposited 2023/09/12 · crossref published-print 2023/10/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28 · crossref indexed 2026/07/31
Blood-brain barrier (BBB) efflux transporters' overexpression hinders antiepileptic drug brain entry. Breast cancer resistance protein (BCRP) is a major BBB efflux transporter. In the present work, BCRP's role as a mechanism that might contribute to drug-resistant epilepsy (DRE) in a mouse model of acute seizures was studied with further assessment of the effect of its inhibition by ko143 and metformin (MET) on lamotrigine (LTG) bioavailability and efficacy. 42 male mice divided into 6 groups: G1: Normal control, G2: LTG-injected healthy mice: LTG 20 mg/kg i.p., G3: Acute seizures (A.S) mice: Pentylenetetrazole (PTZ) 50 mg/kg i.p., G4: LTG-treated A.S mice: LTG 20 mg/kg + PTZ 50 mg/kg i.p., G5: Ko143 + LTG treated A.S mice: Ko143 15 mg/kg i.p. before LTG + PTZ, G6: MET + LTG treated A.S mice: MET 200 mg/kg i.p. before LTG + PTZ. Seizures severity, serum, brain LTG, and brain BCRP were assessed. PTZ group experienced the highest seizure frequency and brain BCRP expression. Ko143 and MET groups showed a significant decrease in brain BCRP with subsequent improvement in brain LTG level and better seizure control. BCRP has a significant role in epilepsy resistance and its inhibition with ko143 or MET adds value to DRE management.