Basic and Clinical Neuroscience Journal
مجله علوم اعصاب پایه و بالینی
BCN
Medical Sciences
http://bcn.iums.ac.ir
137
journal137
2008-126X
2228-7442
10.32598/bcn
en
jalali
1402
6
1
gregorian
2023
9
1
14
5
online
1
fulltext
en
Expressional Study of Permeability Glycoprotein and Multidrug Resistance Protein 1 in Drug-resistant Mesial Temporal Lobe Epilepsy
Cellular and molecular Neuroscience
Cellular and molecular Neuroscience
Original
Original
<div style="text-align: justify;"><strong>Introduction</strong>: About 30% of patients with epilepsy do not respond to anti-epileptic drugs, leading to refractory seizures. The pathogenesis of drug-resistance in mesial temporal lobe epilepsy (MTLE) is not completely understood. Increased activity of drug-efflux transporters might be involved, resulting in subclinical concentrations of the drug at the target site. The major drug-efflux transporters are permeability glycoprotein (P-gp) and multidrug-resistance associated protein-1 (MRP-1). The major drawback so far is the expressional analysis of transporters in equal numbers of drug-resistant epileptic tissue and age-matched non-epileptic tissue.<br>
<strong>Methods</strong>: We have studied P-gp and MRP-1 drug-efflux transporters in the sclerotic hippocampal tissues resected from the epilepsy surgery patients (n=15) and compared their expression profile with the tissues resected from non-epileptic autopsy cases (n=15).<br>
<strong>Results</strong>: Statistically significant over expression of both P-gp (P<0.0001) and MRP-1 (P=0.01) at gene and protein levels were found in the MTLE cases. The fold change of P-gp was more pronounced than MRP-1. Immunohistochemistry of the patient group showed increased immunoreactivity of P-gp at blood-brain barrier and increased reactivity of MRP-1 in the parenchyma. The results were confirmed by confocal immunofluorescence microscopy.<br>
<strong>Conclusion</strong>: Our results suggested that P-gp in association with MRP-1 might be responsible for the multi-drug resistance in epilepsy. P-gp and MRP-1 could be important determinants of bio availability and tissue distribution of anti-epileptic drugs in the brain which can pharmacologically inhibited to achieve optimal drug penetration to target site.</div>
Drug-efflux transporters, Drug-resistant epilepsy, Mesial temporal lobe epilepsy (MTLE), Permeability glycoprotein (P-gp), Multi-drug resistance 1 (MDR1), Multidrug resistance protein 1 (MRP1)
615
630
http://bcn.iums.ac.ir/browse.php?a_code=A-10-2554-3&slc_lang=en&sid=1
Mandeep
Kaur
kaurmandeephg@gmail.com
13700319475328460046663
13700319475328460046663
No
Department of Anatomy, Institute of Medical Education and Research, Chandigarh, India.
Tulika
Gupta
tulikag11@gmail.com
13700319475328460046664
13700319475328460046664
Yes
Department of Anatomy, Institute of Medical Education and Research, Chandigarh, India.
Mili
Gupta
miligupta8@yahoo.com
13700319475328460046665
13700319475328460046665
No
Department of Biochemistry, Singh Judge Institute of Dental Sciences and Hospital, Panjab University, Chandigarh, India.
Navneet
Singla
drnavi2007@yahoo.co.in
13700319475328460046666
13700319475328460046666
No
Department of Neurosurgery, Institute of Medical Education and Research, Chandigarh, India.
Parampreet S
Kharbanda
neuroparam@hotmail.com
13700319475328460046667
13700319475328460046667
No
Department of Neurology, Institute of Medical Education and Research, Chandigarh, India.
Yogender Singh
Bansal
yogendrabansal@hotmail.com
13700319475328460046668
13700319475328460046668
No
Department of Forensic Medicine, Institute of Medical Education and Research, Chandigarh, India.
Daisy
Sahni
daisy_sahni@rediffmail.com
13700319475328460046669
13700319475328460046669
No
Department of Anatomy, Institute of Medical Education and Research, Chandigarh, India.
Bishan Das
Radotra
bishanradotra@gmail.com
13700319475328460046670
13700319475328460046670
No
Department of Histopathology, Institute of Medical Education and Research, Chandigarh, India.
Sunil Kumar
Gupta
13700319475328460046671
13700319475328460046671
No
Department of Neurosurgery, Institute of Medical Education and Research, Chandigarh, India.