Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama, Japan.
Immunopharmacol Immunotoxicol. 2012 Apr;34(2):216-21. doi: 10.3109/08923973.2011.595417. Epub 2011 Aug 19.
Brain oxidative reactions are involved in epilepsy as well as neurodegenerative diseases. In animal convulsion models, some anticonvulsants have been found to suppress oxidative reactions associated with convulsions. However, the effect of anticonvulsants on brain oxidative reactions has not fully been clarified.
Midazolam and phenobarbital are often used as an intravenous anesthetic, and are known to have anticonvulsive effect, but antioxidative effect of these drugs has rarely been studied. Thus, the purpose of this study was to evaluate the effects of these drugs on the degree of convulsions and brain oxidative reactions in an animal convulsion model.
In order to evaluate brain oxidative reactions, we measured malondialdehyde (MDA) level and heme oxygenase (HO)-1 mRNA expression level in the brain of mice in a convulsion model generated by a single injection of pentylenetetrazole (PTZ). We evaluated the effects of midazolam and phenobarbital on the degree of PTZ-induced convulsions and on the changes in brain MDA level and HO-1 mRNA expression level.
After PTZ injection, severe convulsions were observed in all mice. MDA level was increased in the whole brain, while HO-1 mRNA expression level was increased only in the hippocampus. Both midazolam and phenobarbital prevented the convulsions and suppressed the increase in both MDA level and HO-1 mRNA expression level in the brain.
In this study, both midazolam and phenobarbital suppressed PTZ-induced MDA and HO-1 reactions in the brain, suggesting that these drugs inhibit brain oxidative reactions in a convulsion model.
脑氧化反应与癫痫和神经退行性疾病有关。在动物惊厥模型中，一些抗惊厥药已被发现可抑制与惊厥相关的氧化反应。然而，抗惊厥药对脑氧化反应的影响尚未完全阐明。
咪达唑仑和苯巴比妥常被用作静脉麻醉剂，已知具有抗惊厥作用，但这些药物的抗氧化作用很少被研究。因此，本研究旨在评估这些药物在动物惊厥模型中对惊厥程度和脑氧化反应的影响。
为了评估脑氧化反应，我们测量了戊四氮（PTZ）单次注射诱导惊厥模型中小鼠脑内丙二醛（MDA）水平和血红素加氧酶（HO）-1 mRNA 表达水平。我们评估了咪达唑仑和苯巴比妥对 PTZ 诱导惊厥程度以及脑 MDA 水平和 HO-1 mRNA 表达水平变化的影响。
PTZ 注射后，所有小鼠均出现严重惊厥。全脑 MDA 水平升高，而海马区 HO-1 mRNA 表达水平升高。咪达唑仑和苯巴比妥均可预防惊厥，并抑制脑 MDA 水平和 HO-1 mRNA 表达水平的升高。
在这项研究中，咪达唑仑和苯巴比妥均抑制了 PTZ 诱导的脑 MDA 和 HO-1 反应，表明这些药物在惊厥模型中抑制了脑氧化反应。
