Ganzella Marcelo, Jardim Fluvia M, Boeck Carina R, Vendite Deusa
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Neurosci Res. 2006 Aug;55(4):397-402. doi: 10.1016/j.neures.2006.05.003.
The excitotoxicity induced by QA has been related to its ability to increase free radical content and oxidative stress. In order to investigate the time course of toxicity and oxidative profile in the mice hippocampus following seizures induced by QA infusion (36.8 nM, i.c.v.), we evaluated the cellular damage (PI uptake assay), content of ROS formation (DCF assay) and the total radical antioxidant potential (TRAP) and reactivity (TAR) levels. The present results showed that a cellular damage occurred as early as 4 h after QA infusion coincident with an increase in the ROS contents, which returned to control levels after 24 h, while the cellular damage persisted for 72 h. There was a marked increased in the total antioxidant capacity at 8 h after QA infusion in both reactivity and potential levels. By 72 h post-treatment, the TRAP levels decreased, but the TAR levels remained augmented. Therefore, the delayed and persistent increase in the antioxidant capacity after QA insult may be a cellular adaptative response, probably contributing to decrease the ROS levels in order to prevent the spreading of the cellular damage. Therefore, the increase in the QA level in the brain ventricle may induce oxidative stress, which is followed by a persistent response in the antioxidant system in the hippocampus. The present study may, therefore, contribute to elucidate the mechanism of the brain dysfunction in patients with several neurological disorders involving elevation of QA in the CSF.
喹啉酸（QA）诱导的兴奋毒性与其增加自由基含量和氧化应激的能力有关。为了研究脑室内注射QA（36.8 nM）诱导癫痫发作后小鼠海马体中毒性和氧化状态的时间进程，我们评估了细胞损伤（碘化丙啶摄取试验）、活性氧生成量（二氯荧光素试验）以及总自由基抗氧化能力（TRAP）和反应性（TAR）水平。目前的结果表明，QA注射后4小时就出现了细胞损伤，同时活性氧含量增加，24小时后恢复到对照水平，而细胞损伤持续了72小时。QA注射后8小时，反应性和潜在水平的总抗氧化能力均显著增加。到治疗后72小时，TRAP水平下降，但TAR水平仍然升高。因此，QA损伤后抗氧化能力的延迟和持续增加可能是一种细胞适应性反应，可能有助于降低活性氧水平，以防止细胞损伤的扩散。因此，脑室中QA水平的升高可能会诱导氧化应激，随后海马体中的抗氧化系统会出现持续反应。因此，本研究可能有助于阐明脑脊液中QA升高的几种神经疾病患者脑功能障碍的机制。
