Chemistry & Biochemistry, University of Windsor, 401 Sunset Ave, Windsor, ON, Canada.
BMC Neurosci. 2014 Jan 31;15:21. doi: 10.1186/1471-2202-15-21.
Paraquat, still used as an herbicide in some parts of the world, is now regarded as a dangerous environmental neurotoxin and is linked to the development Parkinson's disease (PD). Paraquat interacts with cellular redox systems and causes mitochondrial dysfunction and the formation of reactive oxygen species, which in turn, plays a crucial role in the pathophysiology of PD. Various antioxidant therapies have been explored with the expectations that they deliver health benefits to the PD patients, however, no such therapies were effective. Here we have tested the neuroprotective efficacy of a novel water-soluble CoQ10 (Ubisol-Q10), in a rat model of paraquat-induced neurodegeneration in order to evaluate its potential application in the management of PD.
We have developed a rat model of progressive nigrostriatal degeneration by giving rats five intraperitoneal injections of paraquat (10 mg/kg/injection), once every five days. Neuronal death occurred over a period of 8 weeks with close to 50% reduction in the number of tyrosine hydroxylase-positive cells. Ubisol-Q10, at 6 mg CoQ10/kg body weight/day, was delivered as a supplement in drinking water. The intervention begun after the completion of paraquat injections when the neurodegenerative process had already began and about 20% of TH-positive neurons were lost. Ubisol-Q10 treatment halted the progression of neurodegeneration and remaining neurons were protected. The outcomes were evaluated based on the number of surviving tyrosine hydroxylase-positive neurons in the substantia nigra region and improved motor skills in response to the Ubisol-Q10 intervention. To maintain this neuroprotection, however, continuous Ubisol- Q10 supplementation was required, if withdrawn, the neuronal death pathway resumed, suggesting that the presence of CoQ10 was essential for blocking the pathway.
The CoQ10, given orally as Ubisol-Q10 in drinking solution, was effective in blocking the progression of neurodegeneration when administered therapeutically (post-toxin injection), at a much lower concentration than other previously tested oil soluble formulations and well within the acceptable daily intake of 12 mg/kg/day. Such unprecedented neuroprotection has never been reported before. These results are very encouraging and suggest that Ubisol-Q10 should be further tested and developed as a therapy for halting the progression of PD.
百草枯仍在世界某些地区被用作除草剂，现在被认为是一种危险的环境神经毒素，与帕金森病（PD）的发展有关。百草枯与细胞氧化还原系统相互作用，导致线粒体功能障碍和活性氧的形成，这反过来在 PD 的病理生理学中起着至关重要的作用。已经探索了各种抗氧化疗法，期望它们能为 PD 患者带来健康益处，然而，没有任何一种疗法是有效的。在这里，我们测试了新型水溶性 CoQ10（Ubisol-Q10）在百草枯诱导的神经退行性大鼠模型中的神经保护功效，以评估其在 PD 管理中的潜在应用。
我们通过给大鼠五次腹腔注射百草枯（10 mg/kg/注射），每五天一次，建立了一个进行性黑质纹状体变性的大鼠模型。神经元死亡发生在 8 周的时间内，酪氨酸羟化酶阳性细胞的数量减少了近 50%。Ubisol-Q10 以 6 mg CoQ10/kg 体重/天的剂量作为补充剂添加到饮用水中。干预始于百草枯注射完成后，此时神经退行性过程已经开始，大约 20%的 TH 阳性神经元丢失。Ubisol-Q10 治疗阻止了神经退行性的进展并保护了剩余的神经元。结果基于黑质区域存活的酪氨酸羟化酶阳性神经元的数量以及对 Ubisol-Q10 干预的运动技能改善来评估。然而，为了维持这种神经保护作用，需要持续补充 Ubisol-Q10，如果停止，神经元死亡途径就会恢复，这表明 CoQ10 的存在对于阻断该途径是必不可少的。
口服 CoQ10 作为 Ubisol-Q10 以饮用溶液形式给予时，在治疗性给药（毒素注射后）时有效阻止了神经退行性的进展，其浓度远低于其他以前测试过的油溶性制剂，并且在可接受的每日摄入量 12 mg/kg/天内。这种前所未有的神经保护作用以前从未有过报道。这些结果非常令人鼓舞，表明 Ubisol-Q10 应该进一步测试和开发，作为阻止 PD 进展的治疗方法。
