Expression of Multidrug Resistance Genes in Peripheral Blood of Patients with Refractory Epilepsy and the Reverse Effect of Oxcarbazepine on Its Expression
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Abstract
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.
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| Issue | Vol 47 No 1 (2018) | |
| Section | Original Article(s) | |
| Keywords | ||
| Refractory epilepsy Multidrug resistance gene Multidrug resistance-associated protein 1 | ||
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