scholarly journals Nintedanib decreases muscle fibrosis and improves muscle function in a murine model of dystrophinopathy

2018 ◽  
Vol 9 (7) ◽  
Author(s):  
Patricia Piñol-Jurado ◽  
Xavier Suárez-Calvet ◽  
Esther Fernández-Simón ◽  
Eduard Gallardo ◽  
Natalia de la Oliva ◽  
...  
Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2295
Author(s):  
Paola Mantuano ◽  
Gianluca Bianchini ◽  
Ornella Cappellari ◽  
Brigida Boccanegra ◽  
Elena Conte ◽  
...  

Background: Branched-chain amino acids (BCAAs: leucine, isoleucine, valine) account for 35% of skeletal muscle essential amino acids (AAs). As such, they must be provided in the diet to support peptide synthesis and inhibit protein breakdown. Although substantial evidence has been collected about the potential usefulness of BCAAs in supporting muscle function and structure, dietary supplements containing BCAAs alone may not be effective in controlling muscle protein turnover, due to the rate-limiting bioavailability of other AAs involved in BCAAs metabolism. Methods: We aimed to evaluate the in vivo/ex vivo effects of a 4-week treatment with an oral formulation containing BCAAs alone (2:1:1) on muscle function, structure, and metabolism in a murine model of physiological exercise, which was compared to three modified formulations combining BCAAs with increasing concentrations of L-Alanine (ALA), an AA controlling BCAAs catabolism. Results: A preliminary pharmacokinetic study confirmed the ability of ALA to boost up BCAAs bioavailability. After 4 weeks, mix 2 (BCAAs + 2ALA) had the best protective effect on mice force and fatigability, as well as on muscle morphology and metabolic indices. Conclusion: Our study corroborates the use of BCAAs + ALA to support muscle health during physiological exercise, underlining how the relative BCAAs/ALA ratio is important to control BCAAs distribution.


Author(s):  
D. Bracey ◽  
J.S. Willey ◽  
E.A. Tallant ◽  
P.D. Gallagher ◽  
T.L. Smith ◽  
...  

2022 ◽  
Author(s):  
Carolyn Tallon ◽  
Anjali Sharma ◽  
Zhi Zhang ◽  
Ajit G. Thomas ◽  
Justin Ng ◽  
...  

2015 ◽  
Vol 24 (9) ◽  
pp. 1887-1900 ◽  
Author(s):  
Hyun Ju Lim ◽  
Sunyoung Joo ◽  
Seh-Hoon Oh ◽  
John D. Jackson ◽  
Delrae M. Eckman ◽  
...  

2018 ◽  
Vol 116 ◽  
pp. 30-42 ◽  
Author(s):  
Priscila A.C. Valadão ◽  
Matheus P.S.M. Gomes ◽  
Bárbara C. Aragão ◽  
Hermann A. Rodrigues ◽  
Jéssica N. Andrade ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Xia Dong ◽  
Tiankun Hui ◽  
Jie Chen ◽  
Zheng Yu ◽  
Dongyan Ren ◽  
...  

Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disease characterized by progressive muscle weakness and wasting. Stimulation of AMP-activated protein kinase (AMPK) has been demonstrated to increase muscle function and protect muscle against damage in dystrophic mice. Metformin is a widely used anti-hyperglycemic drug and has been shown to be an indirect activator of AMPK. Based on these findings, we sought to determine the effects of metformin on neuromuscular deficits in mdx murine model of DMD. In this study, we found metformin treatment increased muscle strength accompanied by elevated twitch and tetanic force of tibialis anterior (TA) muscle in mdx mice. Immunofluorescence and electron microscopy analysis of metformin-treated mdx muscles revealed an improvement in muscle fiber membrane integrity. Electrophysiological studies showed the amplitude of miniature endplate potentials (mEPP) was increased in treated mice, indicating metformin also improved neuromuscular transmission of the mdx mice. Analysis of mRNA and protein levels from muscles of treated mice showed an upregulation of AMPK phosphorylation and dystrophin-glycoprotein complex protein expression. In conclusion, metformin can indeed improve muscle function and diminish neuromuscular deficits in mdx mice, suggesting its potential use as a therapeutic drug in DMD patients.


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