Department of Physiology, Faculty of Medicine, University of Ondokuz Mayis, 55139 Samsun, Turkey.
Seizure. 2010 Mar;19(2):102-8. doi: 10.1016/j.seizure.2009.12.005. Epub 2010 Jan 20.
Ascorbic acid and nitric oxide are known to play important roles in epilepsy. The aim of present study was to identify the involvement of nitric oxide (NO) in the anticonvulsant effects of ascorbic acid on penicillin-induced epileptiform activity in rats. Intracortical injection of penicillin (500, International Units (IU)) into the left sensorimotor cortex induced epileptiform activity within 2-5 min. Thirty minutes after penicillin injection, nitric oxide synthase (NOS) inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME, 100mg/kg), neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (7-NI, 40 mg/kg), NO substrate, l-arginine (500 mg/kg) were administered with the most effective dose of ascorbic acid (100 mg/kg) intraperitoneally (i.p.). The administration of l-arginine significantly decreased the frequency of epileptiform activity while administration of l-NAME did not influence the mean frequency of epileptiform activity. Injection of 7-NI decreased the mean frequency of epileptiform activity but did not influence amplitude. Ascorbic acid decreased both the mean frequency and amplitude of penicillin-induced epileptiform activity in rats. The application of l-NAME partially and temporarily reversed the anticonvulsant effects of ascorbic acid. The results support the hypothesis of neuro-protective role for NO and ascorbic acid. The protective effect of ascorbic acid against epileptiform activity was partially and temporarily reversed by nonspecific nitric oxide synthase inhibitor l-NAME, but not selective neuronal nitric oxide synthase inhibitor 7-NI, indicating that ascorbic acid needs endothelial-NOS/NO route to decrease penicillin-induced epileptiform activity.
抗坏血酸和一氧化氮已知在癫痫中起重要作用。本研究的目的是确定一氧化氮（NO）在抗坏血酸对青霉素诱导的大鼠皮质癫痫样活动的抗惊厥作用中的作用。将青霉素（500 国际单位（IU））注入左侧感觉运动皮质内，可在 2-5 分钟内引起癫痫样活动。在青霉素注射后 30 分钟，给予一氧化氮合酶（NOS）抑制剂 N（G）-硝基-L-精氨酸甲酯（l-NAME，100mg/kg），神经元型一氧化氮合酶（nNOS）抑制剂 7-硝基吲唑（7-NI，40mg/kg），NO 底物 L-精氨酸（500mg/kg），并腹腔内给予最有效的抗坏血酸剂量（100mg/kg）。给予 L-精氨酸可显著降低癫痫样活动的频率，而给予 l-NAME 则不影响癫痫样活动的平均频率。7-NI 的注射降低了癫痫样活动的平均频率，但不影响振幅。抗坏血酸降低了青霉素诱导的大鼠癫痫样活动的平均频率和振幅。应用 l-NAME 部分和暂时逆转了抗坏血酸的抗惊厥作用。结果支持 NO 和抗坏血酸具有神经保护作用的假说。非特异性一氧化氮合酶抑制剂 l-NAME 部分和暂时逆转了抗坏血酸对癫痫样活动的保护作用，但选择性神经元型一氧化氮合酶抑制剂 7-NI 则没有，表明抗坏血酸需要内皮型一氧化氮合酶/NO 途径来降低青霉素诱导的癫痫样活动。
