La maladie de Parkinson au Canada (serveur d'exploration)

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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

Identifieur interne : 000987 ( Main/Exploration ); précédent : 000986; suivant : 000988

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

Auteurs : Krithika Muthukumaran [Canada] ; Samantha Leahy [Canada] ; Kate Harrison [Canada] ; Marianna Sikorska [Canada] ; Jagdeep K. Sandhu [Canada] ; Jerome Cohen [Canada] ; Corrine Keshan [Canada] ; Daniel Lopatin [Canada] ; Harvey Miller [Canada] ; Henryk Borowy-Borowski [Canada] ; Patricia Lanthier [Canada] ; Shelly Weinstock [États-Unis] ; Siyaram Pandey [Canada]

Source :

RBID : PMC:3917573

English descriptors

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.


Url:
DOI: 10.1186/1471-2202-15-21
PubMed: 24483602
PubMed Central: 3917573


Affiliations:


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Le document en format XML

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<name sortKey="Lanthier, Patricia" sort="Lanthier, Patricia" uniqKey="Lanthier P" first="Patricia" last="Lanthier">Patricia Lanthier</name>
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</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="I2">Psychology, University of Windsor, Windsor, ON, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Psychology, University of Windsor, Windsor, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series>
<title level="j">BMC Neuroscience</title>
<idno type="eISSN">1471-2202</idno>
<imprint>
<date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Administration, Oral</term>
<term>Animals</term>
<term>Cell Survival (drug effects)</term>
<term>Feasibility Studies</term>
<term>Male</term>
<term>Neurons (drug effects)</term>
<term>Neurons (pathology)</term>
<term>Neuroprotective Agents (administration & dosage)</term>
<term>Neuroprotective Agents (chemistry)</term>
<term>Paraquat</term>
<term>Parkinson Disease (physiopathology)</term>
<term>Parkinson Disease (prevention & control)</term>
<term>Rats</term>
<term>Rats, Long-Evans</term>
<term>Rifabutin (analogs & derivatives)</term>
<term>Solubility</term>
<term>Substantia Nigra (drug effects)</term>
<term>Substantia Nigra (pathology)</term>
<term>Substantia Nigra (physiopathology)</term>
<term>Treatment Outcome</term>
<term>Ubiquinone (administration & dosage)</term>
<term>Ubiquinone (analogs & derivatives)</term>
<term>Ubiquinone (chemistry)</term>
<term>Vitamins (administration & dosage)</term>
<term>Vitamins (chemistry)</term>
<term>Water (chemistry)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en">
<term>Neuroprotective Agents</term>
<term>Ubiquinone</term>
<term>Vitamins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en">
<term>Rifabutin</term>
<term>Ubiquinone</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en">
<term>Neuroprotective Agents</term>
<term>Ubiquinone</term>
<term>Vitamins</term>
<term>Water</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>Cell Survival</term>
<term>Neurons</term>
<term>Substantia Nigra</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en">
<term>Neurons</term>
<term>Substantia Nigra</term>
</keywords>
<keywords scheme="MESH" qualifier="physiopathology" xml:lang="en">
<term>Parkinson Disease</term>
<term>Substantia Nigra</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en">
<term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Administration, Oral</term>
<term>Animals</term>
<term>Feasibility Studies</term>
<term>Male</term>
<term>Paraquat</term>
<term>Rats</term>
<term>Rats, Long-Evans</term>
<term>Solubility</term>
<term>Treatment Outcome</term>
</keywords>
</textClass>
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</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<sec>
<title>Background</title>
<p>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 CoQ
<sub>10</sub>
(Ubisol-Q
<sub>10</sub>
), in a rat model of paraquat-induced neurodegeneration in order to evaluate its potential application in the management of PD.</p>
</sec>
<sec>
<title>Results</title>
<p>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-Q
<sub>10</sub>
, at 6 mg CoQ
<sub>10</sub>
/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-Q
<sub>10</sub>
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-Q
<sub>10</sub>
intervention. To maintain this neuroprotection, however, continuous Ubisol- Q
<sub>10</sub>
supplementation was required, if withdrawn, the neuronal death pathway resumed, suggesting that the presence of CoQ
<sub>10</sub>
was essential for blocking the pathway.</p>
</sec>
<sec>
<title>Conclusion</title>
<p>The CoQ
<sub>10</sub>
, given orally as Ubisol-Q
<sub>10</sub>
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-Q
<sub>10</sub>
should be further tested and developed as a therapy for halting the progression of PD.</p>
</sec>
</div>
</front>
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<name sortKey="Bogdanov, M" uniqKey="Bogdanov M">M Bogdanov</name>
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<name sortKey="Browne, Se" uniqKey="Browne S">SE Browne</name>
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<author>
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<author>
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<author>
<name sortKey="Bui, T" uniqKey="Bui T">T Bui</name>
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<author>
<name sortKey="Miles, L" uniqKey="Miles L">L Miles</name>
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<author>
<name sortKey="Quinlan, J" uniqKey="Quinlan J">J Quinlan</name>
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<author>
<name sortKey="Wong, B" uniqKey="Wong B">B Wong</name>
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<author>
<name sortKey="Wenisch, A" uniqKey="Wenisch A">A Wenisch</name>
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<author>
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<name sortKey="Laplante, S" uniqKey="Laplante S">S Laplante</name>
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<name sortKey="Maswood, N" uniqKey="Maswood N">N Maswood</name>
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<author>
<name sortKey="Young, J" uniqKey="Young J">J Young</name>
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<author>
<name sortKey="Tilmont, E" uniqKey="Tilmont E">E Tilmont</name>
</author>
<author>
<name sortKey="Zhang, Z" uniqKey="Zhang Z">Z Zhang</name>
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<author>
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<author>
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<author>
<name sortKey="Grondin, R" uniqKey="Grondin R">R Grondin</name>
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<author>
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</author>
<author>
<name sortKey="Mattison, J" uniqKey="Mattison J">J Mattison</name>
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<author>
<name sortKey="Lane, Ma" uniqKey="Lane M">MA Lane</name>
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<author>
<name sortKey="Carson, Re" uniqKey="Carson R">RE Carson</name>
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<author>
<name sortKey="Cohen, Rm" uniqKey="Cohen R">RM Cohen</name>
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<author>
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</author>
<author>
<name sortKey="Quigley, C" uniqKey="Quigley C">C Quigley</name>
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<author>
<name sortKey="Ingram, K" uniqKey="Ingram K">K Ingram</name>
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<author>
<name sortKey="Kalehua, An" uniqKey="Kalehua A">AN Kalehua</name>
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<author>
<name sortKey="Muth, Nj" uniqKey="Muth N">NJ Muth</name>
</author>
<author>
<name sortKey="Hengemihle, Jm" uniqKey="Hengemihle J">JM Hengemihle</name>
</author>
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<name sortKey="Jucker, M" uniqKey="Jucker M">M Jucker</name>
</author>
<author>
<name sortKey="Calhoun, Me" uniqKey="Calhoun M">ME Calhoun</name>
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<author>
<name sortKey="Ingram, Dk" uniqKey="Ingram D">DK Ingram</name>
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<li>Canada</li>
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</country>
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<name sortKey="Borowy Borowski, Henryk" sort="Borowy Borowski, Henryk" uniqKey="Borowy Borowski H" first="Henryk" last="Borowy-Borowski">Henryk Borowy-Borowski</name>
<name sortKey="Cohen, Jerome" sort="Cohen, Jerome" uniqKey="Cohen J" first="Jerome" last="Cohen">Jerome Cohen</name>
<name sortKey="Cohen, Jerome" sort="Cohen, Jerome" uniqKey="Cohen J" first="Jerome" last="Cohen">Jerome Cohen</name>
<name sortKey="Harrison, Kate" sort="Harrison, Kate" uniqKey="Harrison K" first="Kate" last="Harrison">Kate Harrison</name>
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<name sortKey="Keshan, Corrine" sort="Keshan, Corrine" uniqKey="Keshan C" first="Corrine" last="Keshan">Corrine Keshan</name>
<name sortKey="Keshan, Corrine" sort="Keshan, Corrine" uniqKey="Keshan C" first="Corrine" last="Keshan">Corrine Keshan</name>
<name sortKey="Lanthier, Patricia" sort="Lanthier, Patricia" uniqKey="Lanthier P" first="Patricia" last="Lanthier">Patricia Lanthier</name>
<name sortKey="Leahy, Samantha" sort="Leahy, Samantha" uniqKey="Leahy S" first="Samantha" last="Leahy">Samantha Leahy</name>
<name sortKey="Leahy, Samantha" sort="Leahy, Samantha" uniqKey="Leahy S" first="Samantha" last="Leahy">Samantha Leahy</name>
<name sortKey="Lopatin, Daniel" sort="Lopatin, Daniel" uniqKey="Lopatin D" first="Daniel" last="Lopatin">Daniel Lopatin</name>
<name sortKey="Lopatin, Daniel" sort="Lopatin, Daniel" uniqKey="Lopatin D" first="Daniel" last="Lopatin">Daniel Lopatin</name>
<name sortKey="Miller, Harvey" sort="Miller, Harvey" uniqKey="Miller H" first="Harvey" last="Miller">Harvey Miller</name>
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<name sortKey="Sandhu, Jagdeep K" sort="Sandhu, Jagdeep K" uniqKey="Sandhu J" first="Jagdeep K" last="Sandhu">Jagdeep K. Sandhu</name>
<name sortKey="Sikorska, Marianna" sort="Sikorska, Marianna" uniqKey="Sikorska M" first="Marianna" last="Sikorska">Marianna Sikorska</name>
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