Ayyildiz Mustafa, Yildirim Mehmet, Agar Erdal
Department of Physiology, Faculty of Medicine, University of Ondokuz Mayis, 55139 Samsun, Turkey.
Epilepsy Res. 2007 Feb;73(2):166-72. doi: 10.1016/j.eplepsyres.2006.09.007. Epub 2006 Nov 7.
A variety of animal seizure models exist which help to document the effects of alpha-tocopherol (Vitamin E) and specify its action. In the present study, we provide further evidence for the functional involvement of NO in the anticonvulsant effects of alpha-tocopherol on penicillin-induced epileptiform electrocorticographical (ECoG) activity in rats. The epileptiform ECoG activity was induced by microinjection of penicillin into the left sensorimotor cortex. Thirty minutes after penicillin injection, the most effective dose of alpha-tocopherol (500 mg/kg) was administrated intramuscularly (i.m.). Alpha-tocopherol decreased the frequency of penicillin-induced epileptiform ECoG activity without changing the amplitude. The effect of systemic administration of nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) and NO substrates, L-arginine and sodium nitro prusside (SNP) on anticonvulsive effects of alpha-tocopherol was investigated. The administration of L-NAME (60 mg/kg, i.p.) did not influence the frequency of epileptiform ECoG activity while administration of L-arginine (500 mg/kg, i.p.) and SNP (6 mg/kg, i.p.) significantly decreased in the penicillin-treated group. The administration of L-NAME (60 mg/kg, i.p.) 10 min after alpha-tocopherol (500 mg/kg, i.m.) application reversed the anticonvulsant effects of alpha-tocopherol. The administration of L-arginine (500 mg/kg, i.p.) and SNP (6 mg/kg, i.p.) did not affect the frequency of epileptiform ECoG activity in alpha-tocopherol supplemented group. L-arginine and SNP did not provide an additional anticonvulsant effect in alpha-tocopherol supplemented group. These results support the involvement of the nitric oxide pathway in the anticonvulsant effect of alpha-tocopherol on the penicillin-induced epileptiform ECoG activity.
存在多种动物癫痫模型，这些模型有助于记录α-生育酚（维生素E）的作用并明确其作用机制。在本研究中，我们进一步证明了一氧化氮（NO）在α-生育酚对青霉素诱导的大鼠癫痫样脑电图（ECoG）活动的抗惊厥作用中发挥功能性作用。通过将青霉素微量注射到左侧感觉运动皮层来诱导癫痫样ECoG活动。青霉素注射30分钟后，肌肉注射（i.m.）最有效的α-生育酚剂量（500mg/kg）。α-生育酚降低了青霉素诱导的癫痫样ECoG活动的频率，而不改变其幅度。研究了全身给予一氧化氮合酶（NOS）抑制剂NG-硝基-L-精氨酸甲酯（L-NAME）以及NO底物L-精氨酸和硝普钠（SNP）对α-生育酚抗惊厥作用的影响。给予L-NAME（60mg/kg，腹腔注射）对癫痫样ECoG活动频率没有影响，而给予L-精氨酸（500mg/kg，腹腔注射）和SNP（6mg/kg，腹腔注射）在青霉素治疗组中显著降低了癫痫样ECoG活动频率。在应用α-生育酚（500mg/kg，肌肉注射）10分钟后给予L-NAME（60mg/kg，腹腔注射）可逆转α-生育酚的抗惊厥作用。在补充α-生育酚的组中，给予L-精氨酸（500mg/kg，腹腔注射）和SNP（6mg/kg，腹腔注射）对癫痫样ECoG活动频率没有影响。在补充α-生育酚的组中，L-精氨酸和SNP没有提供额外的抗惊厥作用。这些结果支持一氧化氮途径参与α-生育酚对青霉素诱导的癫痫样ECoG活动的抗惊厥作用。
