Nehru Bimla, Verma Ranjeet, Khanna Pooja, Sharma Suresh Kumar
Department of Biophysics, Panjab University, Chandigarh-160014, India.
Brain Res. 2008 Mar 27;1201:122-7. doi: 10.1016/j.brainres.2008.01.074. Epub 2008 Feb 9.
Rotenone, a potent specific inhibitor of mitochondrial complex-1, appears to reproduce the behavioral features of Parkinson's disease in rats. It destroys dopaminergic neurons selectively, causing deficiency of dopamine in striatum which leads to impaired motor functions. Oxidative stress generated as a result of mitochondrial dysfunction and metabolism of dopamine has been implicated as an important factor in the etiology of Parkinson's disease. Present study explores the potential of centrophenoxine (a well known anti-aging and antioxidant drug) against rotenone induced motor dysfunction. Sprague Dawley male rats were administered with rotenone on a daily basis by subcutaneous injection of dose: 2 mg/kg body weight over a period of 35 days. Data showed impaired motor function, significant increase in catalepsy, decrease in locomotor activity and decrease in muscle activity. Dopamine content of rotenone treated animals was found to decrease significantly and lipid peroxidation was found to increase significantly in rotenone treated animals when compared with co-treated group. Co-treatment with centrophenoxine (100 mg/kg i.p. for 35 days) significantly attenuated the extent of motor dysfunction and changes in the level of dopamine and lipid peroxidation induced by rotenone toxicity. Thus, the present study provides evidence that centrophenoxine co-treatment attenuates rotenone induced motor dysfunction by virtue of its antioxidant action.
鱼藤酮是线粒体复合物I的一种强效特异性抑制剂，它似乎能在大鼠身上重现帕金森病的行为特征。它选择性地破坏多巴胺能神经元，导致纹状体中多巴胺缺乏，进而导致运动功能受损。线粒体功能障碍和多巴胺代谢产生的氧化应激被认为是帕金森病病因中的一个重要因素。本研究探讨了甲氯芬酯（一种著名的抗衰老和抗氧化药物）对抗鱼藤酮诱导的运动功能障碍的潜力。通过皮下注射剂量为2毫克/千克体重的鱼藤酮，每天对斯普拉格-道利雄性大鼠进行给药，持续35天。数据显示运动功能受损、僵住症显著增加、运动活动减少以及肌肉活动减少。与联合治疗组相比，发现鱼藤酮处理的动物多巴胺含量显著降低，且鱼藤酮处理的动物脂质过氧化显著增加。与甲氯芬酯联合治疗（腹腔注射100毫克/千克，持续35天）显著减轻了鱼藤酮毒性诱导的运动功能障碍程度以及多巴胺水平和脂质过氧化的变化。因此，本研究提供了证据表明，甲氯芬酯联合治疗凭借其抗氧化作用减轻了鱼藤酮诱导的运动功能障碍。
