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研究鱼藤酮诱导的生化变化与脑区神经肌肉协调相关的大脑损伤在大鼠中的相关性。

A study to correlate rotenone induced biochemical changes and cerebral damage in brain areas with neuromuscular coordination in rats.

机构信息

Division of Toxicology, Central Drug Research Institute (CSIR), Lucknow 226001 (U.P.), India.

出版信息

Toxicology. 2010 Jun 4;272(1-3):17-22. doi: 10.1016/j.tox.2010.03.019. Epub 2010 Apr 3.

Abstract

Rotenone induces neurotoxicity but its correlation with biochemical and cerebral changes in rat brain regions are not well defined. In the present study rotenone was administered (3, 6 and12mug/mul) intranigrally in adult male SD rats and its effect was assessed on neuromuscular coordination and in different brain areas viz. striatum (STR), mid-brain (MB), frontal cortex (FC) and hippocampus (HP) cerebral and biochemical changes on 1st and 7th day after treatment. All the doses of rotenone significantly impaired neuromuscular coordination performance on Rota rod test on 1st and 7th day. TTC staining showed significant increase in cerebral injury volume on 1st and 7th day after rotenone treatment indicating mitochondrial enzyme deficiency but increase after 7th day was less that after 1st day. Rotenone treated rats showed significant decrease in GSH and increase in MDA in different brain regions though the pattern was varied. After 1 day of rotenone (6 and 12mug) treatment significant decrease in GSH was observed in STR and MB while MDA was significantly increased only in MB. The maximal effect on GSH and MDA was obtained in STR and MB on 7th day after treatment with 12mug dose of rotenone. Thus, based on the occurrence of changes, it may be suggested that impairment of neuromuscular coordination is inked to oxidative stress rather than mitochondrial enzyme deficiency, all the processes are correlated with each other with the progression of time. MB appeared as most sensitive brain area towards rotenone toxicity.

摘要

鱼藤酮诱导神经毒性,但它与大鼠脑区生化和大脑变化的相关性尚不清楚。在本研究中,鱼藤酮(3、6 和 12μg/μl)被脑内给药于成年雄性 SD 大鼠,并在第 1 天和第 7 天评估其对神经肌肉协调以及不同脑区(纹状体、中脑、额皮质和海马)的影响。鱼藤酮的所有剂量在第 1 天和第 7 天都显著损害了旋转棒测试中的神经肌肉协调性能。TTC 染色显示,鱼藤酮处理后第 1 天和第 7 天大脑损伤体积显著增加,表明线粒体酶缺乏,但第 7 天的增加少于第 1 天。鱼藤酮处理的大鼠在不同脑区的 GSH 显著减少,MDA 增加,尽管模式不同。鱼藤酮(6 和 12μg)处理后第 1 天,STR 和 MB 中的 GSH 显著减少,而 MDA 仅在 MB 中显著增加。在第 7 天用 12μg 鱼藤酮处理后,STR 和 MB 中 GSH 和 MDA 的最大效应。因此,根据变化的发生,可以认为神经肌肉协调的损害与氧化应激有关,而不是与线粒体酶缺乏有关,所有过程都随着时间的推移相互关联。MB 似乎是对鱼藤酮毒性最敏感的脑区。

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