Bashkatova Valentina, Alam Mesbah, Vanin Anatoly, Schmidt Werner J
Institute of Pharmacology, Russian Academy of Medical Sciences, 125315, Russia.
Exp Neurol. 2004 Apr;186(2):235-41. doi: 10.1016/j.expneurol.2003.12.005.
The complex I inhibitor rotenone is a neurotoxin that has been proposed to induce Parkinson-like degeneration. As the mechanisms of rotenone toxicity are not fully understood, the present study addresses the question of whether rotenone induces NO production and lipid peroxidation-like products, that is, thiobarbituric acid reactive substances (TBARS). Rotenone at a dose of 1.5 mg kg(-1) i.p. was administered to rats daily for 10, 20, 30, and 60 days, and NO and TBARS were measured in the frontal cortex and in the striatum. On the 1st and 10th day, there were no increases in NO and TBARS levels, after 20 days, the NO and TBARS levels were increased in the striatum. After 30 and 60 days, NO and TBARS levels were increased in striatum and frontal cortex. Behaviorally, on days 30 and 60, the rats exhibited akinesia and rigidity in the catalepsy test. These results show that chronic administration of rotenone over a long period is capable of increasing NO and TBARS in the cortex and striatum and mimics Parkinson's disease (PD)-like behavioral symptoms that are akinesia and rigidity in rats.
复合体I抑制剂鱼藤酮是一种神经毒素,有人提出它会诱发帕金森样变性。由于鱼藤酮毒性的机制尚未完全了解,本研究探讨了鱼藤酮是否会诱导一氧化氮(NO)生成以及脂质过氧化样产物,即硫代巴比妥酸反应性物质(TBARS)的问题。以1.5毫克/千克体重的剂量腹腔注射鱼藤酮,每日给大鼠注射,持续10、20、30和60天,然后测量额叶皮质和纹状体中的NO和TBARS。在第1天和第10天,NO和TBARS水平没有升高,20天后,纹状体中的NO和TBARS水平升高。30天和60天后,纹状体和额叶皮质中的NO和TBARS水平均升高。在行为方面,在第30天和第60天,大鼠在僵住症测试中表现出运动不能和僵硬。这些结果表明,长期慢性给予鱼藤酮能够增加皮质和纹状体中的NO和TBARS,并模拟大鼠帕金森病(PD)样的行为症状,即运动不能和僵硬。