The relationship between expression of drug resistance proteins and antiepileptic drug concentrations in brain tissue of patients with refractory epilepsy

Abstract

Objective To compare the expression and distribution of drug resistance proteins P-glycoprotein (P-gp) and lung resistance protein (LRP) in brain tissues of patients with refractory epilepsy and to investigate the relationship between expression of drug resistance proteins and concentration of antiepileptic drug carbamazepine (CBZ). Methods We included the brain tissues of 26 cases with refractory epilepsy who had in the experiment. They had following pathologic diagnosis: focal cortical dysplasia (FCD)Ⅰb(n=10), FCDⅡa(n=4), FCDⅡb(n=2) and brain tumorsincluding ganglioglioma(n=6) and dysembryoplastic neuroepithelial tumor(n=4). Immunohistochemistry staining using EnVision system was used to reveal the expression location of P-gp and LRP, and Western blot in SDS-polyacrylamide gel was used to quantitatively analyze the expression of P-gp and LRP. Fluorescence polarization immunoassay was used to determine concentration of CBZ. Results Both P-gp and LRP performed (μg/ml) prominent overexpression in brain tissues of patients with refractory epilepsy, especially in the lesions of both FCD type Ⅱ （P-gp : 2.593±0.829 vs 1.711±0.292, t=-2.201，P=0.028；LRP: 1.352±0.445 vs 1.179±0.593, t=-2.516，P=0.028, respectively）and tumor（P-gp:1.567±0.092 vs 0.775±0.101, t=2.698， P=0.024；LRP:1.091±0.239 vs 0.825±0.297，t=3.997，P=0.003 respectively）. The concentration of CBZ in lesions of brain tumors were lower than which in surrounding regions（0.848±0.726 vs 0.948±0.785, t=-3.056，P=0.014）, while P-gp and LRP were higher than which in surrounding regions in 80% cases. There was no relationship between expression of drug resistance proteins and concentration of CBZ. Conclusions In processing of drug resistance, P-gp and LRP play important roles. However, there is no correlation between expression of drug resistance proteins and concentration of CBZ, suggesting epilepsy drug resistance to be a complicated mechanism. Key words: Epilepsy; P-Glycoprotein; Carbamazepine; Vault ribonucleoprotein particles