Creatine supplementation reduces skeletal muscle degeneration and enhances mitochondrial function in mdx mice.
The mdx mouse serves as animal model for Duchenne muscular dystrophy. Energy status in muscles of mdx mice is impaired and we have demonstrated recently that the energy precursor creatine exerts beneficial effects on mdx skeletal muscle cells in culture. Here we show that feeding a creatine-enriched diet to new-born mdx mice strongly reduced the first wave of muscle necrosis four weeks after birth. Necrosis of the fast-twitch muscle extensor digitorum longus was inhibited by 63+/-14% (P<0.0001) while necrosis of the slow-twitch soleus muscle was not significantly decreased. In addition, using chemically skinned muscle fibres, we found that mitochondrial respiration capacity was decreased by about 25% in mdx-derived fibres and that long-term creatine-feeding restored respiration to wild-type levels. These results provide evidence that creatine supplementation in mdx mice improves muscle health and may provide a scientific basis for its use as adjuvant therapy in Duchenne muscular dystrophy.
Passaquin
Anne-Catherine
AC
Pharmacology Group, School of Pharmacy, University of Lausanne, 1015 Lausanne, Switzerland.
Renard
Mathilde
M
Kay
Laurence
L
Challet
Corinne
C
Mokhtarian
Armand
A
Wallimann
Theo
T
Ruegg
Urs T
UT
D000818:Animals; D003401:Creatine / Q000008:administration & dosage / Q000627:therapeutic use*; D019587:Dietary Supplements; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D009136:Muscular Dystrophies / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D010101:Oxygen Consumption / Q000187:drug effects
D003401:Creatine