Nitric oxide donors improve prednisone effects on muscular dystrophy in the mdx mouse diaphragm

Wataru Mizunoya, Ritika Upadhaya, Frank J. Burczynski, Guqi Wang, Judy E. Anderson

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

In Duchenne muscular dystrophy (DMD), palliative glucocorticoid therapy can produce myopathy or calcification. Since increased nitric oxide synthase activity in dystrophic mice promotes regeneration, the outcome of two nitric oxide (NO) donor drugs, MyoNovin (M) and isosorbide dinitrate (I), on the effectiveness of the anti-inflammatory drug prednisone (P) in alleviating progression of dystrophy was tested. Dystrophic mdx mice were treated (18 days) as controls or with an NO donor ± P. Fiber permeability and DNA synthesis were labeled by Evans blue dye (EBD) and bromodeoxyuridine uptake, respectively. P decreased body weight gain, M increased quadriceps mass, and I increased heart mass. P increased fiber permeability (%EBD+ fibers) and calcification in diaphragm. Treatment with NO donors ± P (M+P, I+P) reduced %EBD+ fibers and calcification vs. P alone. %EBD+ fibers in M+P diaphragm did not differ from control. NO donor treatment reduced proliferation and the population of c-met+ cells and accelerated fiber regeneration. Concurrent with P, NO donor treatment suppressed two important detrimental effects of P in mice, possibly by accelerating regeneration, rebalancing satellite cell quiescence and activation in dystrophy, and/or increasing perfusion. Results suggest that NO donors could improve current therapy for DMD.

Original languageEnglish
Pages (from-to)C1065-C1077
JournalAmerican Journal of Physiology - Cell Physiology
Volume300
Issue number5
DOIs
Publication statusPublished - May 1 2011

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Inbred mdx Mouse
Nitric Oxide Donors
Muscular Dystrophies
Prednisone
Diaphragm
Evans Blue
Coloring Agents
Regeneration
Duchenne Muscular Dystrophy
Permeability
Isosorbide Dinitrate
Muscular Diseases
Bromodeoxyuridine
Therapeutics
Palliative Care
Nitric Oxide Synthase
Pharmaceutical Preparations
Glucocorticoids
Weight Gain
Anti-Inflammatory Agents

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

Cite this

Nitric oxide donors improve prednisone effects on muscular dystrophy in the mdx mouse diaphragm. / Mizunoya, Wataru; Upadhaya, Ritika; Burczynski, Frank J.; Wang, Guqi; Anderson, Judy E.

In: American Journal of Physiology - Cell Physiology, Vol. 300, No. 5, 01.05.2011, p. C1065-C1077.

Research output: Contribution to journalArticle

Mizunoya, Wataru ; Upadhaya, Ritika ; Burczynski, Frank J. ; Wang, Guqi ; Anderson, Judy E. / Nitric oxide donors improve prednisone effects on muscular dystrophy in the mdx mouse diaphragm. In: American Journal of Physiology - Cell Physiology. 2011 ; Vol. 300, No. 5. pp. C1065-C1077.
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