Ubiquinol-10 ameliorates mitochondrial encephalopathy associated with CoQ deficiency.
Biochim Biophys Acta
; 1842(7): 893-901, 2014 Jul.
Article
en En
| MEDLINE
| ID: mdl-24576561
ABSTRACT
Coenzyme Q10 (CoQ10) deficiency (MIM 607426) causes a mitochondrial syndrome with variability in the clinical presentations. Patients with CoQ10 deficiency show inconsistent responses to oral ubiquinone-10 supplementation, with the highest percentage of unsuccessful results in patients with neurological symptoms (encephalopathy, cerebellar ataxia or multisystemic disease). Failure in the ubiquinone-10 treatment may be the result of its poor absorption and bioavailability, which may be improved by using different pharmacological formulations. In a mouse model (Coq9(X/X)) of mitochondrial encephalopathy due to CoQ deficiency, we have evaluated oral supplementation with water-soluble formulations of reduced (ubiquinol-10) and oxidized (ubiquinone-10) forms of CoQ10. Our results show that CoQ10 was increased in all tissues after supplementation with ubiquinone-10 or ubiquinol-10, with the tissue levels of CoQ10 with ubiquinol-10 being higher than with ubiquinone-10. Moreover, only ubiquinol-10 was able to increase the levels of CoQ10 in mitochondria from cerebrum of Coq9(X/X) mice. Consequently, ubiquinol-10 was more efficient than ubiquinone-10 in increasing the animal body weight and CoQ-dependent respiratory chain complex activities, and reducing the vacuolization, astrogliosis and oxidative damage in diencephalon, septum-striatum and, to a lesser extent, in brainstem. These results suggest that water-soluble formulations of ubiquinol-10 may improve the efficacy of CoQ10 therapy in primary and secondary CoQ10 deficiencies, other mitochondrial diseases and neurodegenerative diseases.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Ataxia
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Ubiquinona
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Encefalomiopatías Mitocondriales
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Debilidad Muscular
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Enfermedades Mitocondriales
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Mitocondrias
Tipo de estudio:
Risk_factors_studies
Idioma:
En
Revista:
Biochim Biophys Acta
Año:
2014
Tipo del documento:
Article