Dietary NaCl supplementation prevents muscle necrosis in a mouse model of Duchenne muscular dystrophy.
The mdx mouse is an animal model for Duchenne muscular dystrophy. Mdx mice fed a 12% NaCl diet from birth up to 20 days of age (mdx-Na mice) had an approximately 50% reduction in serum creatine kinase (CK) activity compared with mdx mice fed a standard diet. Most notably, necrotic fibers in tibialis anterior (TA) muscle of mdx-Na mice were reduced by 99% and were similar in control mice. These mdx mice displayed significantly elevated blood Ca2+ and Na+ levels, while the total calcium content of their TA muscle was reduced to the level of control mice. In addition, mdx-Na mice had elevated zinc and magnesium contents in their TA muscle. These results suggest that elevated serum Na+ leads to Ca2+ extrusion from muscle via the Na+/Ca2+ exchanger causing a decrease in intracellular Ca2+ levels and an increase in blood Ca2+ levels. Extracellular Ca2+ and, in addition, Zn2+ and Mg2+ might also contribute to the stabilization of the cell membrane. Other possibilities explaining the surprisingly efficacious beneficial effect of dietary sodium exist and are discussed.
Yoshida
Mizuko
M
Department of Degenerative Neurological Disease, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8052, Japan. yoshidam@ncnp.go.jp
Yonetani
Akira
A
Shirasaki
Toshihiro
T
Wada
Keiji
K
D000375:Aging; D000818:Animals; D002118:Calcium / Q000097:blood / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D005260:Female; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology*; D020388:Muscular Dystrophy, Duchenne / Q000178:diet therapy / Q000473:pathology*; D009336:Necrosis / Q000517:prevention & control*; D011188:Potassium / Q000097:blood / Q000378:metabolism; D012964:Sodium / Q000097:blood / Q000378:metabolism; D012965:Sodium Chloride / Q000008:administration & dosage* / Q000494:pharmacology*; D015032:Zinc / Q000378:metabolism
D012965:Sodium Chloride; D012964:Sodium; D003402:Creatine Kinase; D015032:Zinc; D011188:Potassium; D002118:Calcium