Orally delivered water soluble Coenzyme Q10 (Ubisol-Q10) blocks on-going neurodegeneration in rats exposed to paraquat: potential for therapeutic application in Parkinson’s disease
Authors: Jerome Cohen
Kate Harrison
Daniel Lopatin
Jagdeep K Sandhu
Shelly Weinstock
Samantha Leahy
Marianna Sikorska
Harvey Miller
Corrine Keshan
Henryk Borowy-Borowski
Patricia Lanthier
Siyaram Pandey
Krithika Muthukumaran
Journal: BMC Neuroscience (2014)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Paraquat; Parkinson's disease; neurodegeneration; CoQ10; Ubisol-Q10
Affiliations: Chemistry & Biochemistry, University of Windsor, 401 Sunset Ave, Windsor, ON, Canada. .

Abstract:  Background: 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. Results: 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 To maintain this neuroprotection, however, continuous Ubisol- Q10 supplementation was required, if withdrawn, the neuronal death pathway resumed, suggesting that the presence of CoQ10 was essential for blocking the pathway. Conclusion: 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. 

Retracted: No

PubPeer comments:
 Figure 1A appears to have a repeated image, although rotated 90u00b0. *** ![file] , 
 Repeated image in Figure 2B and 3B? Could the authors review and comment? *** ![file] ![file] , 
 #2 There are similar issues with other images, but I will wait for comment from the authors. , 
 #1 Apologies, this is an image from a different paper. I reposted this in a different thread: https: pubpeer.com publications 6DCC9037670DD855DE16341C5842A3#1 , 
 Hereu2019s another example, from 2B and 3B (green boxes). TAM. How many of the authors were aware? *** 2B ![file] *** 3B ![file] , 
 Dear Sir Madam, Thank you for pointing out some oversight mistakes in high mag figures of the papers. Blow are my responses, #1. You did bring this a year ago, and we contacted the Journal office, and have submitted corrected figures for addendum in J. Parkinson s Disease. #2. Repeated image in Figure 2B and 3B on BMC Neuroscience. Thank you for pointing this out. I agree with you observation. In both figures, the it was the same group, PQ2 group: rats were PQ-treated for four weeks, and fed with water. How ever, I agree Krithika should have used a different field to show high magnification figure. We have all this data on Stereologer computer, and will submit a modified figure 3. #5. Hereu2019s another example, from 2B and 3B (green boxes). Thank you again for pointing out this major oversight by me. I am extremely sorry to learn this, the student used high mag pics to show in two figures. I am going through all the data on microscope, and will correct this error shortly and communicate to the Journal for correction. I should not have trusted this this student (who has graduated), but I am in possession of all the data and results are clear. Again, my deep apology, I am working on correcting this with help of a new student, and will provided addendum soon. Thank you again for your efforts. Siyaram Pandey , 
 Correction Published: 20 December 2021 Following publication of the original article [1], it was reported that there was an error in Figs. 2B and 3B. One of the figure panel (PQ2 High Magnification) from Fig. 2B was mistakenly duplicated in Fig. 3B (PQ2 High Magnification) Also a high magnification panel of Fig. 2B (control) was put in in Fig. 3B (PQu2009+u2009Ubisol Q10 4 weeks). We have corrected this error. The corrected versions of Figs. 2B and 3B are included in this erratum. Figure 2B: ![file] Figure 3B: ![file] ,