8-hydroxy-2--deoxyguanosine and Muscular-Dystrophy--Duchenne

To determine whether creatine monohydrate (CrM) supplementation increases strength and fat-free mass (FFM) in boys with Duchenne muscular dystrophy (DD).. Thirty boys with DD (50% were taking corticosteroids) completed a double-blind, randomized, cross-over trial with 4 months of CrM (about 0.10 g/kg/day), 6-week wash-out, and 4 months of placebo. Measurements were completed of pulmonary function, compound manual muscle and handgrip strength, functional tasks, activity of daily living, body composition, serum creatine kinase and gamma-glutamyl transferase activity and creatinine, urinary markers of myofibrillar protein breakdown (3-methylhistidine), DNA oxidative stress (8-hydroxy-2-deoxyguanosine [8-OH-2-dG]), and bone degradation (N-telopeptides).. During the CrM treatment phase, there was an increase in handgrip strength in the dominant hand and FFM (p < 0.05), with a trend toward a loss of global muscle strength (p = 0.056) only for the placebo phase, with no improvements in functional tasks or activities of daily living. Corticosteroid use, but not CrM treatment, was associated with a lower 8-OH-2-dG/creatinine (p < 0.05), and CrM treatment was associated with a reduction in N-telopeptides (p < 0.05).. Four months of CrM supplementation led to increases in FFM and handgrip strength in the dominant hand and a reduction in a marker of bone breakdown and was well tolerated in children with DD.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Body Composition; Child; Collagen; Collagen Type I; Creatine; Creatinine; Cross-Over Studies; Deoxyguanosine; Drug Therapy, Combination; Hand Strength; Humans; Male; Methylhistidines; Muscle, Skeletal; Muscular Dystrophy, Duchenne; Organ Size; Peptides; Prednisone; Pregnenediones; Respiratory Muscles; Spirometry; Treatment Outcome

Inflammation and oxidative stress occurs in muscle of Duchenne muscular dystrophy (DMD). The relationship between a panel of biomarkers and the DMD outcome is necessary to indicate of disease progression and response to rehabilitation programs. The aim was to analyze the connective tissue of muscle of Mdx mice and immunoexpression of MMP-2, MMP-9, and 8-OHdG, which signalizes oxidative stress related to DNA damage. Biceps brachii of male C57BL/10 and C57BL/10-Dmd

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Fibrosis; Gene Expression Regulation, Enzymologic; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Inbred mdx; Muscular Dystrophy, Duchenne

Duchenne muscular dystrophy (DMD) is associated with an increase in oxidative stress. We measured 24 h 8-hydroxy-2'-deoxyguanosine (8-OHdG) excretion in 24 patients with MD (DMD + Becker's MD), 23 with myotonic dystrophy, and 34 healthy controls. The 8-OHdG/creatinine ratio was higher in patients with dystrophinopathy ( upward arrow 48%, p <.01) but not myotonic dystrophy, as compared to healthy controls. These results indicate that 8-OHdG excretion can be used as a marker of oxidative stress in clinical trials with dystrophinopathy.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Body Weight; Case-Control Studies; Child; Creatine; Deoxyguanosine; Female; Humans; Male; Muscular Dystrophy, Duchenne; Myotonic Dystrophy; Oxidative Stress