Chronotolerance study of the antiepileptic drug valproic acid in mice.
Chronotolerance study of the antiepileptic drug valproic acid in mice.
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DOI：
10.1186/1740-3391-10-3
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发表时间：
2012-05-10
影响因子：
--
通讯作者：
Boughattas, Naceur A
中科院分区：
文献类型：
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作者：
Ben-Cherif, Wafa;Dridi, Ichrak;Boughattas, Naceur A
背景：丙戊酸（VPA）是一种抗癫痫药物，广泛用于治疗失神性癫痫发作和全身性强直-阵挛性癫痫发作。本研究旨在研究在24小时尺度下，vpa诱导的毒性是否随给药时间的变化而变化。方法：以120只瑞士雄性小鼠为实验对象，观察不同给药时间对VPA耐受性的影响。首次测定VPA平均致死剂量为850±0.2mg/kg, i.p。按6个昼夜节律阶段（1、5、9、13、17和21 Hours After Light Onset， HALO），共给药90只小鼠（15只/昼夜节律时间）；对照组30只（5只/昼夜）。结果：存活的治疗小鼠在直肠温度和体重减轻方面表现出显著的昼夜变化
BACKGROUND: Valproic acid (VPA) is an antiepileptic drug widely used for the treatment of absence seizures and generalized tonic-clonic seizures. The present work aims to study whether VPA-induced toxicity varies according to the dosing-time in the 24 hour-scale.METHODS: The influence of dosing-time on tolerance to VPA was investigated in 120 male Swiss mice synchronized under a light-dark cycle (12:12). The mean VPA lethal dose was first determined to be 850±0.2mg/kg, i.p.. Such a dose was administered by i.p. route to a total of 90 mice divided in six circadian stages [1, 5, 9, 13, 17 and 21 Hours After Light Onset (HALO)] (15 mice/circadian time); 30 mice were used as control (5 mice / circadian time).RESULTS: The surviving treated mice exhibited a significant circadian variation in rectal temperature and body weight loss (p