Abstract
BackgroundParaquat, 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.ResultsWe 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 To maintain this neuroprotection, however, continuous Ubisol- Q10 supplementation was required, if withdrawn, the neuronal death pathway resumed, suggesting that the presence of CoQ10 was essential for blocking the pathway.ConclusionThe CoQ10, given orally as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.
Highlights
Paraquat, still used as an herbicide in some parts of the world, is regarded as a dangerous environmental neurotoxin and is linked to the development Parkinson’s disease (PD)
In conclusion we have shown that the PQ rat model of PD we used in the study shows slow progressive loss of DA neurons and mimics what is seen in patients suffering from PD
Our formulation can prevent the death of the remaining neurons in our PD model when administered after the process of neurodegeneration has been triggered and could be an effective therapeutic at any stage of the disease
Summary
Still used as an herbicide in some parts of the world, is regarded as a dangerous environmental neurotoxin and is linked to the development Parkinson’s disease (PD). 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. Parkinson’s disease (PD), the second most common neurodegenerative disorder, is characterised by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) region of the brain. PD affects approximately 1–2% of the population, above the age of 55 and with the steady growth of the ageing population, disease management is a growing concern for neurologists and other physicians. There is no therapy available to halt the progression of this neurodegeneration. It has been possible, to alleviate the symptoms of the disease by providing dopamine replacement. Administration of levodopa is the most commonly utilized treatment for symptomatic relief [2], yet its prolonged application leads to drug induced dyskinesia, which severely affects the patient’s quality of life
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