Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
Toxicol Appl Pharmacol. 2011 Oct 1;256(1):73-82. doi: 10.1016/j.taap.2011.07.015. Epub 2011 Aug 5.
Numerous epidemiological studies have shown an association between pesticide exposure and increased risk of developing Parkinson's diseases. Oxidative stress generated as a result of mitochondrial dysfunction has been implicated as an important factor in the etiology of Parkinson's disease. Previously, we reported that chronic dichlorvos exposure causes mitochondrial impairments and nigrostriatal neuronal death in rats. The present study was designed to test whether Coenzyme Q(10) (CoQ(10)) administration has any neuroprotective effect against dichlorvos mediated nigrostriatal neuronal death, α-synuclein aggregation, and motor dysfunction. Male albino rats were administered dichlorvos by subcutaneous injection at a dose of 2.5 mg/kg body weight over a period of 12 weeks. Results obtained there after showed that dichlorvos exposure leads to enhanced mitochondrial ROS production, α-synuclein aggregation, decreased dopamine and its metabolite levels resulting in nigrostriatal neurodegeneration. Pretreatment by Coenzyme Q(10) (4.5 mg/kg ip for 12 weeks) to dichlorvos treated animals significantly attenuated the extent of nigrostriatal neuronal damage, in terms of decreased ROS production, increased dopamine and its metabolite levels, and restoration of motor dysfunction when compared to dichlorvos treated animals. Thus, the present study shows that Coenzyme Q(10) administration may attenuate dichlorvos induced nigrostriatal neurodegeneration, α-synuclein aggregation and motor dysfunction by virtue of its antioxidant action.
许多流行病学研究表明，农药暴露与帕金森病风险增加之间存在关联。线粒体功能障碍产生的氧化应激被认为是帕金森病发病机制中的一个重要因素。先前，我们报道慢性敌百虫暴露会导致大鼠线粒体损伤和黑质纹状体神经元死亡。本研究旨在测试辅酶 Q(10)(CoQ(10))给药是否对敌百虫介导的黑质纹状体神经元死亡、α-突触核蛋白聚集和运动功能障碍具有神经保护作用。雄性白化大鼠通过皮下注射以 2.5mg/kg 体重的剂量给予敌百虫，持续 12 周。此后获得的结果表明，敌百虫暴露会导致线粒体 ROS 产生增加、α-突触核蛋白聚集、多巴胺及其代谢物水平降低，导致黑质纹状体神经退行性变。与敌百虫处理的动物相比，用辅酶 Q(10)(4.5mg/kg 腹腔注射，持续 12 周)预处理敌百虫处理的动物可显著减轻黑质纹状体神经元损伤的程度，表现为 ROS 产生减少、多巴胺及其代谢物水平增加以及运动功能障碍的恢复。因此，本研究表明，辅酶 Q(10)给药可能通过其抗氧化作用减轻敌百虫诱导的黑质纹状体神经退行性变、α-突触核蛋白聚集和运动功能障碍。
