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Methylene blue prevents methylmalonate-induced seizures and oxidative damage in rat striatum.

机译:亚甲蓝可防止丙二酸甲酯引起的大鼠癫痫发作和大鼠纹状体的氧化损伤。

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摘要

Methylene blue (MB) is a thiazine dye with cationic and lipophilic properties that acts as an electron transfer mediator in the mitochondria. Due to this metabolic improving activity and free radicals scavenging effects, MB has been used in the treatment of methemoglobinemia and ifosfamide-induced encephalopathy. Considering that methylmalonic acidemia consists of a group of inherited metabolic disorders biochemically characterized by impaired mitochondrial oxidative metabolism and reactive species production, we decided to investigate whether MB, protects against the behavioral and neurochemical alterations elicited by the intrastriatal injection of methylmalonate (MMA). In the present study we showed that intrastriatal injection of MB (0.015-1.5nmol/0.5microl) protected against seizures (evidenced by electrographic recording), protein carbonylation and Na(+),K(+)-ATPase inhibition ex vivo induced by MMA (4.5micromol/1.5microl). Furthermore, we investigated whether convulsions elicited by intrastriatal MMA administration are accompanied by striatal protein carbonyl content increase and changes in Na(+),K(+)-ATPase activity in rat striatum. The effect of MB (0.015-1.5nmol/0.5microl) and MMA (4.5micromol/0.5microl) on striatal NO(x) (NO(2) plus NO(3)) content was also evaluated. Statistical analysis revealed that the MMA-induced NO(x) content increase was attenuated by intrastriatal injection of MB and the duration of convulsive episodes correlated with Na(+),K(+)-ATPase inhibition, but not with MMA-induced total protein carbonylation. In view of that MB decreases MMA-induced neurotoxicity assessed by behavioral and neurochemical parameters, the authors suggest that MB may be of value to attenuate neurological deficits of methylmalonic acidemic patients.
机译:亚甲基蓝(MB)是一种具有阳离子和亲脂性质的噻嗪染料,在线粒体中充当电子转移介质。由于这种代谢改善活性和清除自由基的作用,MB已被用于治疗高铁血红蛋白血症和异环磷酰胺诱导的脑病。考虑到甲基丙二酸血症是由一组遗传学异常的生化代谢紊乱组成,其特征在于线粒体氧化代谢和反应性物质生成受损,因此我们决定研究MB是否能抵抗纹状体内注射甲基丙二酸(MMA)引起的行为和神经化学改变。在本研究中,我们显示纹状体内注射MB(0.015-1.5nmol / 0.5microl)可防止癫痫发作(通过电记录记录证明),蛋白羰基化以及MMA诱导的Na(+),K(+)-ATPase抑制(4.5micromol / 1.5microl)。此外,我们调查了纹状体内MMA给药引起的惊厥是否伴随着纹状体蛋白羰基含量的增加以及大鼠纹状体中Na(+),K(+)-ATPase活性的变化。还评估了MB(0.015-1.5nmol / 0.5microl)和MMA(4.5micromol / 0.5microl)对纹状体NO(x)(NO(2)加NO(3))含量的影响。统计分析表明,纹状体内注射MB可以抑制MMA诱导的NO(x)含量增加,而惊厥发作的持续时间与Na(+),K(+)-ATPase抑制相关,而与MMA诱导的总蛋白无关羰基化。考虑到MB可通过行为和神经化学参数评估降低MMA诱导的神经毒性,因此作者认为MB可能对减轻甲基丙二酸血症患者的神经功能缺损具有重要意义。

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