Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

Abstract

Although the support for the use of antioxidants, such as coenzyme Q 10 (CoQ 10 ), to treat Parkinson's disease (PD) comes from the extensive scientific evidence, the results of conducted thus far clinical trials are inconclusive. It is assumed that the efficacy of CoQ 10 is hindered by insolubility, poor bioavailability, and lack of brain penetration. We have developed a nanomicellar formulation of CoQ 10 (Ubisol-Q 10 ) with improved properties, including the brain penetration, and tested its effectiveness in mouse MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) model with the objectives to assess its potential use as an adjuvant therapy for PD. We used a subchronic MPTP model (5-daily MPTP injections), characterized by 50% loss of dopamine neurons over a period of 28 days. Ubisol-Q 10 was delivered in drinking water. Prophylactic application of Ubisol-Q 10 , started 2 weeks before the MPTP exposure, significantly offset the neurotoxicity (approximately 50% neurons died in MPTP group vs. 17% in MPTP+ Ubisol-Q 10 group by day 28). Therapeutic application of Ubisol-Q 10 , given after the last MPTP injection, was equally effective. At the time of intervention on day 5 nearly 25% of dopamine neurons were already lost, but the treatment saved the remaining 25% of cells, which otherwise would have died by day 28. This was confirmed by cell counts, analyses of striatal dopamine levels, and improved animals' motor skill on a beam walk test. Similar levels of neuroprotection were obtained with 3 different Ubisol-Q 10 concentrations tested, that is, 30 mg, 6 mg, or 3 mg CoQ 10 /kg body weight/day, showing clearly that high doses of CoQ 10 were not required to deliver these effects. Furthermore, the Ubisol-Q 10 treatments brought about a robust astrocytic activation in the brain parenchyma, indicating that astroglia played an active role in this neuroprotection. Thus, we have shown for the first time that Ubisol-Q 10 was capable of halting the neurodegeneration already in progress;

PTS micelles for the delivery of hydrophobic methotrexate

“…Polyoxyethanyl-α-tocopheryl sebacate (PTS) is an amphiphilic compound with both hydrophilic (polyethylene glycol, PEG) and hydrophobic (α-tocopherol) properties, separated by an aliphatic spacer (sebacic acid) (Borowy-Borowski et al, 2004;Sikorska et al, 2014). Due to its self-emulsifying properties it undergoes the formation of micelles (Sikorska et al, 2014) with several advantages as solubilizing agents for numerous lipophilic bioactive molecules. Additionally, they possess lack of toxicity, maximum solubilizing ability and stealth properties (Borowy-Borowski et al, 2004;Sikorska et al, 2003).…”

“…Alongside to all the advantages associated to these micelles, the production of PTS by an esterified form of vitamin E (α-tocopherol) reveal additional benefits. This vitamin can be efficiently hydrolysed in vivo, revealing numerous beneficial proprieties, including antioxidant, anti-inflammatory, antithrombotic, hypocholesterolemic and anti-carcinogenic activities (Borowy-Borowski et al, 2004;Duhem et al, 2014;Sikorska et al, 2014). Recent reports demonstrated that vitamin E possess potent antitumorigenic activity by inducing apoptosis in several cancer cell lines (Ghosh and Biswas, 2017).…”

Effects of Propofol on the Liver Oxidative-Antioxidant Balance in a Rat Model of Parkinson’s Disease

“…Using the cellular model of PD, Strathearn et al demonstrated that substances that are rich in anthocyanins might protect neurons from degeneration [24]. Sikorska et al documented similar observations regarding the beneficial effects of antioxidants on the inhibition of neurodegenerative processes [25]. Additionally, other studies have indicated that the consumption of large amounts of vitamin E may protect against the development of PD [26]; however, a study by Weber et al [27] does not prove the benefits of this vitamin.…”

CoQ10 Function and Role in Heart Failure and Ischemic Heart Disease

“…For example, blood lymphocytes isolated from patients with Parkinson's disease have been reported to have a functional CoQ 10 deficiency, assessed by the rate of cell proliferation in the absence and presence of supplemental CoQ 10 (112). Also, animal intervention studies (125,157) and small human trials (153,155,156) reported CoQ 10 supplements to be neuroprotective. Despite this, however, two randomized trials reported no evidence of benefit of CoQ 10 supplements in Parkinson's disease (8,169), and a recent review analyzing randomized controlled trials looking at CoQ 10 in neurodegenerative diseases has NU35CH03-Stocker ARI 4 May 2015 11:42 concluded that there are insufficient data to support the use of CoQ10 in improving motor symptoms.…”