title: Nitric oxide donors improve prednisone effects on muscular dystrophy in the mdx mouse diaphragm.
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.
authors.affiliation: Dept. of Biological Sciences, Faculty of Science, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Wataru
authors.initials: W
authors.lastname: Mizunoya
authors.forename: Ritika
authors.initials: R
authors.lastname: Upadhaya
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Burczynski
authors.forename: Guqi
authors.initials: G
authors.lastname: Wang
authors.forename: Judy E
authors.initials: JE
authors.lastname: Anderson
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002114:Calcinosis / Q000139:chemically induced / Q000517:prevention & control; D003964:Diaphragm / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006140:Guaifenesin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007548:Isosorbide Dinitrate / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000473:pathology; D009135:Muscular Diseases / Q000139:chemically induced / Q000517:prevention & control; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy*; D009566:Nitrates / Q000627:therapeutic use*; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D009929:Organ Size; D011241:Prednisone / Q000009:adverse effects* / Q000627:therapeutic use; D012038:Regeneration / Q000187:drug effects
chemical_list: D009566:Nitrates; D020030:Nitric Oxide Donors; C559737:guaifenesin dinitrate; D006140:Guaifenesin; D007548:Isosorbide Dinitrate; D011241:Prednisone