Effects of lamotrigine on hippocampal expression of P-glycoprotein, major vault protein, and amino acids in rats with chronic epilepsy
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(The Affiliated Hospital of Yanbian University, Yanji 133002, China)

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R-33

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    Abstract:

    Objective To investigate the effects of lamotrigine on P-glycoprotein (PGP) and major vault protein(MVP) expression, and amino acid contents in the hippocampus of rats with chronic epilepsy. Methods Specificpathogen-free male Sprague-Dawley rats were used as model, low-dose lamotrigine (5 mg/ kg), and high-dose lamotrigine(10 mg/ kg) groups. In addition, healthy rats (n = 15) were used as a control group. All groups were intragastricallyadministered the drug for 25 days. Rats in the model and control groups were administered normal saline at a dose of 1 mL/100 g. Behavioral characteristics and body mass of all rats before and after treatment were recorded. Seizure duration andbrain waves after treatment were also recorded. PGP and MVP were detected in the hippocampi by immunohistochemistryand western blot. Aspartate (Asp), glutamate (Glu), and glycine (Gly) contents in hippocampi were detected by highperformanceliquid chromatography. Results Rats in the control group showed normal behaviors, while chronic epilepsymodel group rats exhibited reduced activity, chewing, rhythmic nodding, upward motions of the head and neck, andforelimb clonic seizures; moreover, a few rats exhibited a vertical tail or tail shot. Rats in the two lamotrigine-treated groupsgradually transitioned from early upward motions of the head and neck, and forelimb clonic seizures to piloerection of thehair and mouth and facial muscles, with rare vertical tails or tail shots. Before treatment, body weights of the model groupand two lamotrigine-treated groups were significantly decreased compared with the control group ( P < 0. 05). Aftertreatment, body mass, electroencephalogram frequency, and Gly contents in the hippocampus were significantly decreased( P < 0. 05 ) in the lamotrigine-treated groups compared with the control group; whereas seizure duration,electroencephalogram amplitude, and hippocampal contents of Asp, Glu, PGP, and MVP were increased ( P < 0. 05).Compared with the model group, body mass, electroencephalogram frequency, and Gly contents in the hippocampus weresignificantly increased ( P < 0. 05); whereas seizure duration, electroencephalogram amplitude, and hippocampal contentsof Asp, Glu, PGP, and MVP were significantly decreased ( P < 0. 05) in the two lamotrigine-treated groups in a dosedependentmanner. Conclusions Lamotrigine can be used to treat chronic epilepsy by reducing PGP and MVP, and improving amino acid levels in the hippocampus.

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  • Received:April 04,2019
  • Revised:
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  • Online: October 10,2019
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