Gulhane Military Medical Academy, Faculty of Medicine, Department of Medical Pharmacology, Psychopharmacology Research Unit, Etlik, 06018 Ankara, Turkey.
Brain Res Bull. 2011 Jul 15;85(6):380-4. doi: 10.1016/j.brainresbull.2011.05.001. Epub 2011 May 11.
Parkinson's disease (PD) is a late-onset, progressive and neurodegenerative disorder of unknown etiology. Besides the other therapeutic approaches, new drug options in pharmacotherapy of PD are important. The aim of the present study was to investigate the effects of pioglitazone and retinoic acid, antioxidant and neuroprotective agents, on rotenone-induced model of PD in rats. Adult male Wistar rats (260-373 g) were subjects. Rotenone (2.5mg/kg, sc) was injected to rats for 70 days. At the end of rotenone administration, rats were treated with pioglitazone (10mg/kg, ip) and retinoic acid (1mg/kg, ip) or vehicles for 15 days. Then, rats were tested for evaluation of Parkinson signs by measurement of locomotor activity. In addition, dopamine levels were detected in striatum, hippocampus and hypothalamus in individual groups of control, rotenone and pioglitazone or retinoic acid-treated rats. Rotenone significantly reduced locomotor activity of the rats. It also significantly reduced dopamine levels in striatum and hippocampus, but not hypothalamus. Pioglitazone and retinoic acid reversed in reduction of locomotor activity significantly. Pioglitazone, but not retinoic acid, significantly reversed the reduced striatal dopamine level. Both drugs were ineffective on reduced levels of dopamine in hippocampus. Our results suggest that pioglitazone and retinoic acid have some beneficial effects on rotenone-induced model of PD in rats. Pioglitazone seems to be more effective than retinoic acid. These agents may be helpful for preventing or controlling of some signs of PD.
帕金森病(PD)是一种病因不明的迟发性、进行性和神经退行性疾病。除了其他治疗方法外,药物治疗 PD 的新选择也很重要。本研究旨在探讨吡格列酮和维甲酸(抗氧化和神经保护剂)对鱼藤酮诱导的 PD 大鼠模型的影响。成年雄性 Wistar 大鼠(260-373g)为研究对象。鱼藤酮(2.5mg/kg,sc)注射大鼠 70 天。在鱼藤酮给药结束时,大鼠用吡格列酮(10mg/kg,ip)和维甲酸(1mg/kg,ip)或载体治疗 15 天。然后,通过测量运动活性来测试大鼠的帕金森症状。此外,还检测了各组对照组、鱼藤酮组和吡格列酮或维甲酸治疗组大鼠纹状体、海马和下丘脑的多巴胺水平。鱼藤酮显著降低了大鼠的运动活性。它还显著降低了纹状体和海马中的多巴胺水平,但下丘脑没有。吡格列酮和维甲酸显著逆转了运动活性的降低。吡格列酮而非维甲酸显著逆转了纹状体多巴胺水平的降低。两种药物对海马中降低的多巴胺水平均无效。我们的研究结果表明,吡格列酮和维甲酸对鱼藤酮诱导的 PD 大鼠模型具有一定的有益作用。吡格列酮似乎比维甲酸更有效。这些药物可能有助于预防或控制 PD 的一些症状。