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  • Title: Effect of 21-day exposure of phenobarbital, carbamazepine and phenytoin on P-glycoprotein expression and activity in the rat brain.
    Author: Wen T, Liu YC, Yang HW, Liu HY, Liu XD, Wang GJ, Xie L.
    Journal: J Neurol Sci; 2008 Jul 15; 270(1-2):99-106. PubMed ID: 18440557.
    Abstract:
    Overexpression of P-glycoprotein may be involved in multidrug resistance of epilepsy, but the mechanisms are not clear. The aim of the studies was to investigate whether chronic exposure of antiepileptic drugs (AEDs) increased P-glycoprotein (P-gp) function and expression in brain of rats. Three drugs phenobarbital (PB), phenytion (PHT) and carbamazepine (CBZ) were orally given to rats twice a day for successive 21 days, P-gp activity in brain was assessed using the brain-to-plasma concentration ratios of rhodamine 123 (Rho 123) at 1 h following intravenous administration of 0.2 mg/kg. Immunohistochemistry was also used to analyze P-gp localization in rat brain regions. P-gp levels in the brain regions were further evaluated using western blot. The results showed 21-day exposure of AEDs resulted in significant decrease of tissue-to-plasma concentration ratios of Rho 123 in cerebral cortex and hippocampus without affecting their concentrations in plasma. Immunohistochemistry result showed that up-regulation of the P-gp mainly occurred in capillary endothelial vessels. Western blot result suggested that the protein level of P-gp in cortex and hippocampus of rats exposed to drugs was significantly higher than that of control rats. The P-gp levels were associated with P-gp activity in corresponding rats. All the results verified the hypothesis that chronic exposure of AEDs may increase P-gp function and level in brain of rats.
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