Allopurinol partially prevents disuse muscle atrophy in mice and humans

Abstract Disuse muscle wasting will likely affect everyone in his or her lifetime in response to pathologies such as joint immobilization, inactivity or bed rest. There are no good therapies to treat it. We previously found that allopurinol, a drug widely used to treat gout, protects muscle damage a...

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Autores principales:	Beatriz Ferrando, Mari Carmen Gomez-Cabrera, Andrea Salvador-Pascual, Carlos Puchades, Frederic Derbré, Arlette Gratas-Delamarche, Ludovic Laparre, Gloria Olaso-Gonzalez, Miguel Cerda, Enrique Viosca, Ana Alabajos, Vicente Sebastiá, Angel Alberich-Bayarri, Fabio García-Castro, Jose Viña
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4ddfa8057c844af095a82b7aec54ee81
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spelling	oai:doaj.org-article:4ddfa8057c844af095a82b7aec54ee812021-12-02T16:08:26ZAllopurinol partially prevents disuse muscle atrophy in mice and humans10.1038/s41598-018-21552-12045-2322https://doaj.org/article/4ddfa8057c844af095a82b7aec54ee812018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21552-1https://doaj.org/toc/2045-2322Abstract Disuse muscle wasting will likely affect everyone in his or her lifetime in response to pathologies such as joint immobilization, inactivity or bed rest. There are no good therapies to treat it. We previously found that allopurinol, a drug widely used to treat gout, protects muscle damage after exhaustive exercise and results in functional gains in old individuals. Thus, we decided to test its effect in the prevention of soleus muscle atrophy after two weeks of hindlimb unloading in mice, and lower leg immobilization following ankle sprain in humans (EudraCT: 2011-003541-17). Our results show that allopurinol partially protects against muscle atrophy in both mice and humans. The protective effect of allopurinol is similar to that of resistance exercise which is the best-known way to prevent muscle mass loss in disuse human models. We report that allopurinol protects against the loss of muscle mass by inhibiting the expression of ubiquitin ligases. Our results suggest that the ubiquitin-proteasome pathway is an appropriate therapeutic target to inhibit muscle wasting and emphasizes the role of allopurinol as a non-hormonal intervention to treat disuse muscle atrophy.Beatriz FerrandoMari Carmen Gomez-CabreraAndrea Salvador-PascualCarlos PuchadesFrederic DerbréArlette Gratas-DelamarcheLudovic LaparreGloria Olaso-GonzalezMiguel CerdaEnrique VioscaAna AlabajosVicente SebastiáAngel Alberich-BayarriFabio García-CastroJose ViñaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Beatriz Ferrando Mari Carmen Gomez-Cabrera Andrea Salvador-Pascual Carlos Puchades Frederic Derbré Arlette Gratas-Delamarche Ludovic Laparre Gloria Olaso-Gonzalez Miguel Cerda Enrique Viosca Ana Alabajos Vicente Sebastiá Angel Alberich-Bayarri Fabio García-Castro Jose Viña Allopurinol partially prevents disuse muscle atrophy in mice and humans
description	Abstract Disuse muscle wasting will likely affect everyone in his or her lifetime in response to pathologies such as joint immobilization, inactivity or bed rest. There are no good therapies to treat it. We previously found that allopurinol, a drug widely used to treat gout, protects muscle damage after exhaustive exercise and results in functional gains in old individuals. Thus, we decided to test its effect in the prevention of soleus muscle atrophy after two weeks of hindlimb unloading in mice, and lower leg immobilization following ankle sprain in humans (EudraCT: 2011-003541-17). Our results show that allopurinol partially protects against muscle atrophy in both mice and humans. The protective effect of allopurinol is similar to that of resistance exercise which is the best-known way to prevent muscle mass loss in disuse human models. We report that allopurinol protects against the loss of muscle mass by inhibiting the expression of ubiquitin ligases. Our results suggest that the ubiquitin-proteasome pathway is an appropriate therapeutic target to inhibit muscle wasting and emphasizes the role of allopurinol as a non-hormonal intervention to treat disuse muscle atrophy.
format	article
author	Beatriz Ferrando Mari Carmen Gomez-Cabrera Andrea Salvador-Pascual Carlos Puchades Frederic Derbré Arlette Gratas-Delamarche Ludovic Laparre Gloria Olaso-Gonzalez Miguel Cerda Enrique Viosca Ana Alabajos Vicente Sebastiá Angel Alberich-Bayarri Fabio García-Castro Jose Viña
author_facet	Beatriz Ferrando Mari Carmen Gomez-Cabrera Andrea Salvador-Pascual Carlos Puchades Frederic Derbré Arlette Gratas-Delamarche Ludovic Laparre Gloria Olaso-Gonzalez Miguel Cerda Enrique Viosca Ana Alabajos Vicente Sebastiá Angel Alberich-Bayarri Fabio García-Castro Jose Viña
author_sort	Beatriz Ferrando
title	Allopurinol partially prevents disuse muscle atrophy in mice and humans
title_short	Allopurinol partially prevents disuse muscle atrophy in mice and humans
title_full	Allopurinol partially prevents disuse muscle atrophy in mice and humans
title_fullStr	Allopurinol partially prevents disuse muscle atrophy in mice and humans
title_full_unstemmed	Allopurinol partially prevents disuse muscle atrophy in mice and humans
title_sort	allopurinol partially prevents disuse muscle atrophy in mice and humans
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/4ddfa8057c844af095a82b7aec54ee81
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Allopurinol partially prevents disuse muscle atrophy in mice and humans

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