Laboratory of Physiology and Pharmacology of Federal University of Piauí, Rua Cícero Eduardo, s/n, Junco, Picos, Piauí, 64600-000, Brazil.
Cell Mol Neurobiol. 2010 Apr;30(3):381-7. doi: 10.1007/s10571-009-9460-9. Epub 2009 Oct 2.
In the present study, we investigated the effects of lipoic acid (LA) in the brain oxidative stress caused by pilocarpine-induced seizures in adult rats. Wistar rats were treated with 0.9% saline (i.p., control group), lipoic acid (10 mg/kg, i.p., LA group), pilocarpine (400 mg/kg, i.p., pilocarpine group), and the association of LA (10 mg/kg, i.p.) plus pilocarpine (400 mg/kg, i.p.), 30 min before the administration of LA (LA plus pilocarpine group). After the treatments, all groups were observed for 1 h. The enzyme activities [delta-aminolevulinic dehydratase (delta-ALA-D), glutathione peroxidase (GPx), glutathione reductase (GR), and Na+,K+-ATPase] as well as the glutathione-reduced (GSH) and ascorbic acid (AA) concentrations were measured using spectrophotometric methods, and the results were compared to values obtained from saline and pilocarpine-treated animals. Protective effects of LA were also evaluated on the same parameters. In pilocarpine group, no changes were observed in GPx and GR activities and AA content. Moreover, in the same group, decrease in GSH levels as well as a reduction in delta-ALA-D and Na+,K+-ATPase activities after seizures was observed. In turn, in LA plus pilocarpine group, the appearance of seizures was abolished, and the decreases in delta-ALA-D and Na+,K+-ATPase activities produced by seizures as well as increases in GSH levels and GPx activity were reversed, when compared to the pilocarpine seizing group. The results of the present study demonstrated that preadministration of LA abolished seizure episodes induced by pilocarpine in rat, probably by reducing oxidative stress in rat hippocampus caused by seizures.
在本研究中,我们研究了硫辛酸(LA)对匹鲁卡品诱导的成年大鼠脑氧化应激的影响。Wistar 大鼠用 0.9%生理盐水(ip,对照组)、硫辛酸(10mg/kg,ip,LA 组)、匹鲁卡品(400mg/kg,ip,匹鲁卡品组)和 LA(10mg/kg,ip)联合匹鲁卡品(400mg/kg,ip)预处理,LA 预处理 30min 后给予 LA(LA 联合匹鲁卡品组)。治疗后,所有组均观察 1h。采用分光光度法测定酶活性[δ-氨基酮戊酸脱水酶(δ-ALA-D)、谷胱甘肽过氧化物酶(GPx)、谷胱甘肽还原酶(GR)和 Na+,K+-ATP 酶]以及还原型谷胱甘肽(GSH)和抗坏血酸(AA)浓度,并与生理盐水和匹鲁卡品处理动物的结果进行比较。还评估了 LA 对相同参数的保护作用。在匹鲁卡品组中,GPx 和 GR 活性和 AA 含量没有变化。此外,在同一组中,癫痫发作后观察到 GSH 水平降低以及 δ-ALA-D 和 Na+,K+-ATP 酶活性降低。相反,在 LA 联合匹鲁卡品组中,癫痫发作被消除,并且癫痫发作引起的 δ-ALA-D 和 Na+,K+-ATP 酶活性降低以及 GSH 水平和 GPx 活性增加得到逆转,与匹鲁卡品致痫组相比。本研究结果表明,LA 的预先给药消除了大鼠匹鲁卡品诱导的癫痫发作,这可能是通过降低大鼠海马因癫痫发作引起的氧化应激来实现的。