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拉莫三嗪对BALB/c小鼠免疫调节作用的评估。

Evaluation of immunomodulatory effects of lamotrigine in BALB/c mice.

作者信息

Abu-Rish Eman Y, Elhayek Shada Y, Mohamed Yehia S, Hamad Islam, Bustanji Yasser

机构信息

1Department of Biopharmaceutics and Clinical Pharmacy, School of Pharmacy The University of Jordan, Amman 11942, Jordan.

2Department of Medical Microbiology College of Medicine, University of Dammam, Dammam 31451 PO Box 2114, Saudi Arabia.

出版信息

Acta Pharm. 2017 Dec 20;67(4):543-555. doi: 10.1515/acph-2017-0035.

Abstract

Modulation of the immune system has recently been shown to be involved in the pharmacological effects of old antiepileptic drugs and in the pathogenesis of epilepsy. Therefore, the most recent guidelines for immunotoxicological evaluation of drugs were consulted to investigate the immunomodulatory effects of lamotrigine, a newer antiepileptic drug, in BALB/c mice. These included the in vivo effects of lamotrigine on delayed-type hypersensitivity (DTH) response to sheep red blood cell (SRBC) antigens, hemagglutination titer assays and hematological changes. In vitro effects of lamotrigine on ConA-induced splenocyte proliferation and cytokine secretion were assessed. The results showed that lamotrigine treatment significantly increased the DTH response to SRBC in the mouse model of this study. This was accompanied by a significant increase in relative monocyte and neutrophil counts and in spleen cellularity. Lamotrigine significantly inhibited ConA-induced splenocyte proliferation in vitro and it significantly inhibited IL-2 and TNF-α secretion in ConA-stimulated splenocytes. In conclusion, the results demonstrated significant immunomodulatory effects of lamotrigine in BALB/c mice. These data could expand the understanding of lamotrigine-induced adverse reactions and its role in modulating the immune system in epilepsy.

摘要

最近研究表明,免疫系统的调节与老一代抗癫痫药物的药理作用以及癫痫的发病机制有关。因此,参考了最新的药物免疫毒理学评估指南,以研究新型抗癫痫药物拉莫三嗪对BALB/c小鼠的免疫调节作用。这些研究包括拉莫三嗪对绵羊红细胞(SRBC)抗原迟发型超敏反应(DTH)的体内作用、血凝滴度测定和血液学变化。评估了拉莫三嗪对刀豆蛋白A(ConA)诱导的脾细胞增殖和细胞因子分泌的体外作用。结果表明,在本研究的小鼠模型中,拉莫三嗪治疗显著增强了对SRBC的DTH反应。这伴随着相对单核细胞和中性粒细胞计数以及脾细胞数量的显著增加。拉莫三嗪在体外显著抑制ConA诱导的脾细胞增殖,并显著抑制ConA刺激的脾细胞中白细胞介素-2(IL-2)和肿瘤坏死因子-α(TNF-α)的分泌。总之,结果表明拉莫三嗪在BALB/c小鼠中具有显著的免疫调节作用。这些数据可以扩展对拉莫三嗪引起的不良反应及其在癫痫免疫系统调节中作用的理解。

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