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

• Published in: PloS one 2017-11, Vol.12 (11), p.e0187317
• Main Authors: Terrill, Jessica R, Pinniger, Gavin J, Nair, Keshav V, Grounds, Miranda D, Arthur, Peter G
• Format: Article
• Language: English
• Subjects: Amino acids; Animals; Biocompatibility; Biology and Life Sciences; Clinical trials; Cysteine; Dosage and administration; Drinking water; Drug dosages; Drug therapy; Duchenne muscular dystrophy; Duchenne's muscular dystrophy; Dystrophy; Gangrene; Genetic aspects; Growth; Inflammation; Liver; Medical research; Medicine and Health Sciences; Metabolism; Mice; Mice, Inbred mdx; Muscle strength; Muscles; Muscular dystrophy; Muscular Dystrophy, Animal - drug therapy; Muscular Dystrophy, Animal - pathology; Muscular strength; Neutrophils; Oxidation; Oxidative metabolism; Oxidative stress; Oxidative Stress - drug effects; Physical Sciences; Proteins; Research and Analysis Methods; Rodents; Studies; Sulfur; Taurine; Taurine - therapeutic use
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0187317

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).