Beneficial effects of high dose taurine treatment in juvenile dystrophic mdx mice are offset by growth restriction.

Duchenne Muscular Dystrophy (DMD) is a fatal muscle wasting disease manifested in young boys, for which there is no current cure. We have shown that the amino acid taurine is safe and effective at preventing dystropathology in the mdx mouse model for DMD. This study aimed to establish if treating gr...

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Main Authors: Jessica R Terrill, Gavin J Pinniger, Keshav V Nair, Miranda D Grounds, Peter G Arthur
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5667875?pdf=render
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spelling doaj-0cad4027fc4743789db3584f2a6641562020-11-25T01:46:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-011211e018731710.1371/journal.pone.0187317Beneficial effects of high dose taurine treatment in juvenile dystrophic mdx mice are offset by growth restriction.Jessica R TerrillGavin J PinnigerKeshav V NairMiranda D GroundsPeter G ArthurDuchenne Muscular Dystrophy (DMD) is a fatal muscle wasting disease manifested in young boys, for which there is no current cure. We have shown that the amino acid taurine is safe and effective at preventing dystropathology in the mdx mouse model for DMD. This study aimed to establish if treating growing mdx mice with a higher dose of taurine was more effective at improving strength and reducing inflammation and oxidative stress. Mice were treated with a dose of taurine estimated to be 16 g/kg/day, in drinking water from 1-6 weeks of age, after which in vivo and ex vivo muscle strength was assessed, as were measures of inflammation, oxidative stress and taurine metabolism. While the dose did decrease inflammation and protein oxidation in dystrophic muscles, there was no improvement in muscle strength (in contrast with benefits observed with the lower dose) and growth of the young mice was significantly restricted. We present novel data that a high taurine dose increases the cysteine content of both mdx liver and plasma, a possible result of down regulation of the taurine synthesis pathway in the liver (which functions to dispose of excess cysteine, which is toxic). These data caution that a high dose of taurine can have adverse effects and may be less efficacious than lower taurine doses. Therefore, monitoring of taurine dosage needs to be considered in future pre-clinical trials, in anticipation of using taurine as a clinical therapy for growing DMD boys (and other conditions).http://europepmc.org/articles/PMC5667875?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Jessica R Terrill
Gavin J Pinniger
Keshav V Nair
Miranda D Grounds
Peter G Arthur
spellingShingle Jessica R Terrill
Gavin J Pinniger
Keshav V Nair
Miranda D Grounds
Peter G Arthur
Beneficial effects of high dose taurine treatment in juvenile dystrophic mdx mice are offset by growth restriction.
PLoS ONE
author_facet Jessica R Terrill
Gavin J Pinniger
Keshav V Nair
Miranda D Grounds
Peter G Arthur
author_sort Jessica R Terrill
title Beneficial effects of high dose taurine treatment in juvenile dystrophic mdx mice are offset by growth restriction.
title_short Beneficial effects of high dose taurine treatment in juvenile dystrophic mdx mice are offset by growth restriction.
title_full Beneficial effects of high dose taurine treatment in juvenile dystrophic mdx mice are offset by growth restriction.
title_fullStr Beneficial effects of high dose taurine treatment in juvenile dystrophic mdx mice are offset by growth restriction.
title_full_unstemmed Beneficial effects of high dose taurine treatment in juvenile dystrophic mdx mice are offset by growth restriction.
title_sort beneficial effects of high dose taurine treatment in juvenile dystrophic mdx mice are offset by growth restriction.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2017-01-01
description Duchenne Muscular Dystrophy (DMD) is a fatal muscle wasting disease manifested in young boys, for which there is no current cure. We have shown that the amino acid taurine is safe and effective at preventing dystropathology in the mdx mouse model for DMD. This study aimed to establish if treating growing mdx mice with a higher dose of taurine was more effective at improving strength and reducing inflammation and oxidative stress. Mice were treated with a dose of taurine estimated to be 16 g/kg/day, in drinking water from 1-6 weeks of age, after which in vivo and ex vivo muscle strength was assessed, as were measures of inflammation, oxidative stress and taurine metabolism. While the dose did decrease inflammation and protein oxidation in dystrophic muscles, there was no improvement in muscle strength (in contrast with benefits observed with the lower dose) and growth of the young mice was significantly restricted. We present novel data that a high taurine dose increases the cysteine content of both mdx liver and plasma, a possible result of down regulation of the taurine synthesis pathway in the liver (which functions to dispose of excess cysteine, which is toxic). These data caution that a high dose of taurine can have adverse effects and may be less efficacious than lower taurine doses. Therefore, monitoring of taurine dosage needs to be considered in future pre-clinical trials, in anticipation of using taurine as a clinical therapy for growing DMD boys (and other conditions).
url http://europepmc.org/articles/PMC5667875?pdf=render
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