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J Appl Physiol (1985). 2019 Jul 11. doi: 10.1152/japplphysiol.00162.2019. [Epub ahead of print]

Nutraceutical and pharmaceutical cocktails did not improve muscle function or reduce histological damage in d2-mdx mice.

Author information

1
Department of Animal Science, Iowa State University, United States.
2
Department of Health and Human Performance, University of Montana, United States.

Abstract

Progressive muscle injury and weakness are hallmarks of Duchenne muscular dystrophy. We showed previously that quercetin (Q) partially protected dystrophic limb muscles from disease-related injury. As quercetin activates PGC-1α through Sirtuin-1, an NAD+-dependent deacetylase, the depleted NAD+ in dystrophic skeletal muscle may limit quercetin efficacy, hence, supplementation with the NAD+ donor, nicotinamide riboside (NR), may facilitate quercetin efficacy. Lisinopril (Lis) protects skeletal muscle and improves cardiac function in dystrophin-deficient mice, therefore it was included in this study to evaluate the effects of lisinopril used with quercetin and NR. Our purpose was to determine the extent to which Q, NR, and Lis decreased dystrophic injury. We hypothesized that Q, NR or Lis alone would improve muscle function and decrease histological injury and when used in combination would have additive effects. Muscle function of 11-month-old DBA (healthy), D2-mdx (dystrophin-deficient), and D2-mdx mice was assessed following treatment with Q, NR, and/or Lis for 7-months. To mimic typical pharmacology of DMD patients a group was treated with prednisolone (Pred) in combination with Q, NR and Lis. At 11-months of age, dystrophin deficiency decreased specific tension and tetanic force in the soleus and extensor digitorum longus muscles and was not corrected by any treatment. Dystrophic muscle was more sensitive to contraction-induced injury, which was partially offset in the QNRLisPred group, while fatigue was similar between all groups. Treatments did not decrease histological damage. These data suggest treatment with Q, NR, Lis and Pred failed to adequately maintain dystrophic limb muscle function or decrease histological damage.

KEYWORDS:

ACE inhibitor; DMD; glucocorticoid; prednisolone; quercetin

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