Original Article

Expression of Multidrug Resistance Genes in Peripheral Blood of Patients with Refractory Epilepsy and the Reverse Effect of Oxcarbazepine on Its Expression


Background: We aimed to investigate the expression levels of multidrug resistance gene 1 (MDR1), multidrug resistance-associated protein 1 (MRP1) and multidrug resistance P-glycoprotein (P-gp) in peripheral blood of patients with refractory epilepsy.

Methods: Patients with epilepsy (n=24) and those with refractory epilepsy (n=24) were selected, and 30 normal volunteers were enrolled as control. The expression level of MDR1 genes was detected using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The expression levels of P-gp and MRP1 were detected via Western blotting. The above-mentioned patients with refractory epilepsy were randomly divided into the oxcarbazepine group (OB group) and placebo group (OZ group). After consecutive 8-week oral administration of drugs, the curative effect and adverse reactions of patients with refractory epilepsy were observed, and the life quality of patients was evaluated.

Results: The expression levels of MDR1 genes, P-gp and MRP1 in peripheral blood of patients with refractory epilepsy were significantly increased compared with those of patients with epilepsy, (P<0.05). At 8 weeks after the drug therapy, the effective rate and life quality of patients in OB group were significantly higher than those of patients in OZ group (P<0.01). There was no significant difference in the incidence rate of adverse reactions during the treatment between the two groups. After treatment, the expression levels of MDR1, P-gp and MRP1 in peripheral blood of patients in OB group were significantly lower than those of patients in OZ group (P<0.01).

Conclusion: Oxacillipine could effectively improve the effective treatment rate of patients with refractory epilepsy. The mechanism may be related to MDR1, MRP1 and Pgp expression.




Liu X, Ou S, Xu T et al (2016). New differ-entially expressed genes and differential DNA methylation underlying refractory epilepsy. Oncotarget, 7(52): 87402–87416.

Granata T, Marchi N, Carlton E et al (2009). Management of the patient with medically refractory epilepsy. Expert Rev Neurother, 9(12): 1791-802.

Caciagli L, Bernhardt BC, Hong SJ, Bernas-coni A, Bernasconi N (2014). Functional network alterations and their structural substrate in drug-resistant epilepsy. Front Neurosci, 8:411.

Linda D, Mark JC (2016). Managing drug-resistant epilepsy: challenges and solu-tions. Neuropsychiatr Dis Treat, 12: 2605–2616.

Chambers A, Bowen JM (2016). Electrical Stimulation for Drug-Resistant Epilepsy: An Evidence-Based Analysis. Ont Health Technol Assess Ser, 13(18):1-37.

Cuicui W, Zhen H, Yinghui C (2015). In-volvement of p38 MAPK in the Drug Resistance of Refractory Epilepsy Through the Regulation Multidrug Re-sistance-Associated Protein 1. Neurochem Res, 40(7): 1546–1553.

Pavlidis E, Rubboli G, Nikanorova M, Kölmel MS, Gardella E (2015). Encepha-lopathy with status epilepticus during sleep (ESES) induced by oxcarbazepine in idiopathic focal epilepsy in childhood. Funct Neurol, 30(2):139-41.

Yang W, Huanian Z, Changhe N et al (2014). Population pharmacokinetics modeling of oxcarbazepine to character-ize drug interactions in Chinese children with epilepsy. Acta Pharmacol Sin, 35(10): 1342–1350.

Moon J, Lee ST, Choi J et al (2014). Unique Behavioral Characteristics and microRNA Signatures in a Drug Resistant Epilepsy Model. PLoS One, 9(1): e85617.

Pollard JR, Eidelman O, Mueller GP (2012). The TARC/sICAM5 Ratio in Patient Plasma is a Candidate Biomarker for Drug Resistant Epilepsy. Front Neurol, 3:181.

Ban JJ, Jung KH, Chu K et al (2012). Pro-files of Multidrug Resistance Protein-1 in the Peripheral Blood Mononuclear Cells of Patients with Refractory Epilepsy. PLoS One, 7(5): e36985.

Seven M1, Batar B, Unal S et al (2014). The drug-transporter gene MDR1 C3435T and G2677T/A polymorphisms and the risk of multidrug-resistant epilepsy in Turkish children. Mol Biol Rep, 41(1): 331–336.

Saidijam M, Mahjub H, Shabab N, Yadega-razari R (2015). Simultaneous Analysis of Multidrug Resistance 1(MDR1) C3435T, G2677T/A, and C1236T Genotypes in Hamadan City Population, West of Iran. Iran Biomed J, 19(1): 57–62.

Emich-Widera E, Likus W, Kazek B, Sieroń AL, Urbanek K (2014). Polymorphism of ABCB1/MDR1 C3435T in Children and Adolescents with Partial Epilepsy is due to Different Criteria for Drug Resistance - Preliminary Results. Med Sci Monit, 20:1654-61.

Park HA, Kubicki N, Gnyawali S et al (2011). Natural Vitamin E α-Tocotrienol Protects Against Ischemic Stroke by Induction of Multidrug Resistance-Associated Protein 1. Stroke, 42(8):2308-14.

Liu X, Yue X, Chen S, Chen J, Li R (2015). Significance of the expression of MRP1 and MRP2 in peripheral blood mononu-clear cells of children with intractable epi-lepsy. Exp Ther Med 10(5):1784-1788.

Santucci R, Fothergill H, Laugel V et al (2010). The onset of acute oxcarbazepine toxicity related to prescription of clar-ithromycin in a child with refractory epi-lepsy. Br J Clin Pharmacol, 69(3):314-6.

Pirmohamed M, Graham A, Roberts P et al (2016). Carbamazepine-hypersensitivity: assessment of clinical and in vitro chemi-cal cross-reactivity with phenytoin and oxcarbazepine. Br J Clin Pharmacol, 32(6):741-9.

IssueVol 47 No 1 (2018) QRcode
SectionOriginal Article(s)
Refractory epilepsy Multidrug resistance gene Multidrug resistance-associated protein 1

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
JI J, LI G, MA Y, PAN S, YUAN R. Expression of Multidrug Resistance Genes in Peripheral Blood of Patients with Refractory Epilepsy and the Reverse Effect of Oxcarbazepine on Its Expression. Iran J Public Health. 2017;47(1):40-48.