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Am J Physiol Regul Integr Comp Physiol (September 22, 2005). doi:10.1152/ajpregu.00684.2004
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Submitted on October 5, 2004
Accepted on September 13, 2005

Dietary NaCl supplementation prevents muscle necrosis in a mouse model of Duchenne Muscular Dystrophy

Mizuko Yoshida1*, Akira Yonetani2, Toshihiro Shirasaki2, and Keiji Wada1

1 Department of Degenerative Neurological Disease, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan
2 HITACHI High-technologies Co., Hitachinaka, Ibaragi, Japan

* To whom correspondence should be addressed. E-mail: yoshidam{at}ncnp.go.jp.

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.







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