The effects of ascorbic acid on penicillin-induced epileptiform activity in rats
The effects of ascorbic acid on penicillin-induced epileptiform activity in rats
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DOI：
10.1111/j.1528-1167.2007.01080.x
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发表时间：
2007-07-01
期刊：
影响因子：
5.6
通讯作者：
Agar, Erdal
中科院分区：
文献类型：
--
作者：
Ayyildiz, Mustafa;Coskun, Sule;Agar, Erdal
目的：癫痫发作是由一群过度兴奋的神经元过度放电引起的。许多研究有助于证明活性氧自由基清除剂如α-生育酚或抗坏血酸（维生素C）的作用。在本研究中，我们研究了抗坏血酸的影响，在六个不同的剂量，对青霉素诱导的epileptificationactivity.Methods：一个单一的微量注射青霉素（2.5 μ l，500单位，intricortically）到左侧感觉运动皮层诱导epileptificationactivity在2-5分钟内，进展到完全发作活动持续类似3-5小时。在第一组实验中，注射青霉素后30分钟，腹腔内（IP）给予6种不同剂量的抗坏血酸（25、50、100、200、400或800 mg/kg）。另一组动物接受有效剂量的抗坏血酸（100 mg/kg，IP）7天。青霉素治疗前24小时停止抗坏血酸给药。另一组大鼠在青霉素治疗前30 min接受有效剂量的抗坏血酸（100 mg/kg，IP）。结果：低剂量抗坏血酸（50、100 mg/kg，注射青霉素后30 min）可降低青霉素诱发的大鼠癫痫样活动的频率和幅度，而高剂量抗坏血酸（50、100 mg/kg，注射青霉素后30 min）可降低青霉素诱发的大鼠癫痫样活动的频率和幅度。抗坏血酸，在中等剂量（200，400毫克/公斤，青霉素注射后30分钟），减少癫痫样活动的频率，而不改变振幅。抗坏血酸，在最低剂量（25毫克/公斤）和最高剂量（800毫克/公斤）（青霉素注射后30分钟），没有改变癫痫样活动的频率或幅度。低剂量（100 mg/kg）的抗坏血酸是改变青霉素诱导的癫痫样活动频率和振幅的最有效剂量。在青霉素治疗前30分钟用抗坏血酸（100 mg/kg）预处理引起青霉素诱导的癫痫样活动的发作显著延迟。用抗坏血酸（100 mg/kg）预处理7天并没有改变癫痫样活动的潜伏期。最有效剂量的抗坏血酸（100 mg/kg）防止了青霉素诱导的癫痫样活动后发生的GSH水平的降低和脂质过氧化水平（MDA）的增加。结论：这些数据表明，抗坏血酸对青霉素诱导的癫痫样皮层脑电图活动具有神经保护活性。
Purpose: Epileptic seizure results from excessive discharge in a population of hyperexcitable neurons. A number of studies help to document the effects of active oxygen free radical scavengers such as alpha-tocopherol or ascorbic acid (vitamin C). In the present study, we examined the effects of ascorbic acid, at the six different doses, on penicillin-induced epileptiform activity.Methods: A single microinjection of penicillin (2.5 mu l, 500 units, intracortically) into the left sensorimotor cortex induced epileptiform activity within 2-5 min, progressing to full seizure activity lasting similar to 3-5 h. In the first set of experiments, 30 min after penicillin injection, six different doses of ascorbic acid (25, 50, 100, 200, 400, or 800 mg/kg) were administered intraperitoneally (IP). The other group of animals received the effective dose of ascorbic acid (100 mg/kg, IP) for 7 days. Ascorbic acid administration was stopped 24 h before penicillin treatment. Another group of rats received the effective dose of ascorbic acid (100 mg/kg, IP) 30 min before penicillin treatment. In the second set of experiments, the lipid peroxidation (NIDA) and reduced glutathione (GSH) levels of brain were measured in the control, control + ascorbic acid, penicillin, and penicillin + ascorbic acid groups.Results: Ascorbic acid, at the low dose (50, 100 mg/kg, 30 min after penicillin injection), decreased both the frequency and amplitude of penicillin-induced epileptiform activity in rats. Ascorbic acid, at intermediate doses (200, 400 mg/kg, 30 min after penicillin injection), decreased the frequency of epileptiform activity without changing the amplitude. Ascorbic acid, at the lowest dose (25 mg/kg) and highest dose (800 mg/kg) (30 min after penicillin injection), did not change either the frequency or amplitude of epileptiform activity. Ascorbic acid, at the low dose (100 mg/kg) was the most effective dose in changing the frequency and amplitude of penicillin-induced epileptiform activity. Pretreatment with ascorbic acid (100 mg/kg) 30 min before penicillin treatment caused a significant delay in the onset of penicillin-induced epileptiform activity. Pretreatment with ascorbic acid (100 mg/kg) for 7 days did not change the latency of epileptiform activity. The most effective dose of ascorbic acid (100 mg/kg) prevented both the decrease in GSH level and the increase in lipid peroxidation level (MDA) occurring after penicillin-induced epileptiform activity.Conclusions: These data indicate that ascorbic acid has neuroprotective activity against penicillin-induced epileptiform electrocorticogram activity.