Circulating Nrf2, Glutathione, and Malondialdehyde Correlate with Disease Severity in Duchenne Muscular Dystrophy.

Oxidative stress (OS) plays an essential role in the pathophysiology of Duchenne muscular dystrophy (DMD). However, the actors that regulate OS need to be better studied. We aimed to evaluate whether NFE2-like bZIP transcription factor 2 (Nrf2), glutathione, malondialdehyde (MDA), and protein carbonyl concentrations change according to the disease severity in DMD patients. Moreover, we assessed whether OS correlated with muscle injury, clinical characteristics, physical activity, and antioxidant food consumption (AFC). A total of 28 DMD patients participated in this study. OS markers, metabolic indicators, and enzymatic markers of muscle injury were measured in circulation. Muscle injury was measured with clinical scales, and physical activity and AFC were evaluated with questionnaires. Nrf2 concentration was lower (p ≤ 0.01), and malondialdehyde concentration was higher (p < 0.05) in non-ambulatory patients than in ambulatory patients. Nrf2 correlated with age (rho = -0.387), Vignos scale (rho = -0.328), GMFCS scale (rho = -0.399), and Brooke scale scores (rho = -0.371) (p < 0.05). MDA correlated with Vignos (rho = 0.317) and Brooke scale scores (rho = 0.414) (p ≤ 0.05). In conclusion, DMD patients with the worst muscle function had more significant oxidative damage and lower antioxidant function than DMD patients with better muscle function.

Natural history of circulating miRNAs in Duchenne disease: Association with muscle injury and metabolic parameters.

OBJECTIVES: This study aimed to evaluate whether the expression of circulating dystromiRs and a group of oxidative stress-related (OS-R) miRNAs is associated with muscle injury and circulating metabolic parameters in Duchenne muscular dystrophy (DMD) patients. METHODS: Twenty-four DMD patients were included in this cross-sectional study. Clinical scales to evaluate muscle injury (Vignos, GMFCS, Brooke, and Medical Research Council), enzymatic muscle injury parameters (CPK, ALT, and AST), anthropometry, metabolic indicators, physical activity, serum dystromiRs (miR-1-3p, miR-133a-3p, and miR-206), and OS-R miRNAs (miR-21-5p, miR-31-5p, miR-128-3p, and miR-144-3p) levels were measured in ambulatory and non-ambulatory DMD patients. RESULTS: DystromiRs (except miR-1-3p) and miRNAs OS-R levels were lower (p-value <.05) in the non-ambulatory group than the ambulatory group. The expression of those miRNAs correlated with Vignos scale score (For instance, rho = -0.567, p-value <0.05 for miR-21-5p) and with other scales scores of muscle function and strength. CPK, AST, and ALT concentration correlated with expression of all miRNAs (For instance, rho = 0.741, p-value <.05 between miR-206 level and AST concentration). MiR-21-5p level correlated with glucose concentration (rho = -0.369, p-value = .038), and the miR-1-3p level correlated with insulin concentration (rho = 0.343, p-value = .05). CONCLUSIONS: Non-ambulatory DMD patients have lower circulating dystromiRs and OS-R miRNAs levels than ambulatory DMD patients. The progressive muscle injury is associated with a decrease in the expression of those miRNAs, evidencing DMD progress. These findings add new information about the natural history of DMD.

Circulating markers of oxidative stress are associated with a muscle injury in patients with muscular dystrophy Duchenne.

BACKGROUND: A small number of studies have confirmed the presence of oxidative damage in patients with Duchenne muscular dystrophy (DMD). Nevertheless, it is unknown if there a relationship of circulating markers of oxidative stress with a muscle injury. OBJECTIVE: We evaluated if oxidative damage and anti-oxidant markers are associated with muscle damage in DMD. METHODS: This cross-sectional study included 24 patients with DMD classified in ambulatory and non-ambulatory. Markers of muscle damage (creatine kinase [CK]), oxidative damage (malondialdehyde [MDA], and 8-isoprostane), anti-oxidant function (Thiol and mRNA of NRF2 and NF-κB) and nitric oxide (NO) were quantified in circulation. RESULTS: Total NO, MDA, and 8-isoprostane concentrations were significantly (p < 0.05) higher, and thiol concentration was lower in non-ambulatory than ambulatory patients. A significant correlation (p < 0.05) between muscle injury (evaluated by Vignos scale) with CK (r = -0.382), NO (r = 0.444), MDA (r = 0.503), 8-isoprostanes (r = 0.435) and thiol (r = -0.430) was observed. CONCLUSION: These findings suggest that non-ambulatory have high oxidative damage and low anti-oxidant function than ambulatory patients with DMD. Total nitric oxide and oxidative damage plasma markers increase, but the anti-oxidant marker thiol decreases with a muscle injury in boys with DMD. The findings of this study suggest that these markers could be considered as goods indicators of oxidative damage in longitudinal studies to evaluate the muscle injury during DMD progression. Additionally, these findings add new information about the pathophysiology of DMD.