Functional muscle impairment in facioscapulohumeral muscular dystrophy is correlated with oxidative stress and mitochondrial dysfunction

International audienceFacioscapulohumeral muscular dystrophy (FSHD),the most frequent muscular dystrophy, is an autosomal dominant disease. In most individuals with FSHD, symptoms are restricted to muscles of the face, arms, legs, and trunk. FSHD is genetically linked to contractions of the D4Z4 repeat array causing activation of several genes.One of these maps in the repeat itself and expresses the DUX4 (the double homeobox 4) transcription factor causing a gene deregulation cascade. In addition, analyses of the RNA or protein expression profiles in muscle have indicated deregulations in the oxidative stress response. Since oxidative stress affects peripheral muscle function, we investigated mitochondrial function and oxidative stress in skeletal muscle biopsies and blood samples from patients with FSHD and age-matched healthy controls, and evaluated their association with physical performances.We show that specifically, oxidative stress (lipid peroxidation and protein carbonylation), oxidative damage (lipofuscin accumulation), and antioxidant enzymes (catalase, copper–zinc-dependent super- oxide dismutase, and glutathione reductase) were higher in FSHD than in control muscles. FSHD muscles also presented abnormal mitochondrial function (decreased cytochrome c oxidase activity and reduced ATP synthesis). In addition, the ratio between reduced (GSH) and oxidized glutathione (GSSG) was strongly decreased in all FSHD blood samples as a consequence of GSSG accumulation. Patients with FSHD also had reduced systemic antioxidative response molecules, such as low levels of zinc (a SOD cofactor), selenium (a GPx cofactor involved in the elimination of lipid peroxides), and vitamin C. Half of them had a low ratio of gamma/alpha tocopherol and higher ferritin concentrations. Both systemic oxidative stress and mitochondrial dysfunction were correlated with functional muscle impairment. Mitochondrial ATP production was significantly correlated with both quadriceps endurance (TLimQ) and maximal voluntary contraction (MVCQ) values (rho¼0.79, P¼0.003; rho¼0.62, P¼0.05, respectively). The plasma concentration of oxidized glutathione was negatively correlated with the TLimQ, MVCQ values, and the 2-min walk distance (MWT) values (rho¼0.60, P¼0.03; rho¼0.56, P¼0.04; rho¼0.93, Po0.0001, respectively). Our data characterized oxidative stress in patients with FSHD and demonstrated a correlation with their peripheral skeletal muscle dysfunction. They suggest that antioxidants that might modulate or delay oxidative insult maybe useful in maintaining FSHD muscle functions

Spirulina supplementation prevents exercise-induced lipid peroxidation, inflammation and skeletal muscle damage in elite rugby players

International audienceBACKGROUND: The present study aimed to examine the effects of spirulina supplementation on pro/antioxidant status, inflammation and skeletal muscle damage markers immediately and 24 h after exhaustive exercise in elite rugby players. METHODS: Seventeen elite male Rugby Union players were randomly assigned to a spirulina (SPI: n = 9) or placebo (PLA: n = 8) group in a double-blind design. Subjects were supplemented with Spirulina platensis (5.7 g day(-1) ) or placebo (isoproteic and caloric) for 7 weeks. At baseline and after 7 weeks of supplementation, blood samples were obtained before (T0), immediately after (T1) and 24 h after (T2) exhaustive exercise. The Yoyo Intermittent Recovery Test Level 2 was used as an exhaustive exercise to induce oxidative stress (OS), inflammation and skeletal muscle damage. The studied parameters included pro/antioxidant status markers (superoxide dismutase, glutathione peroxidase, reduced glutathione/glutathione disulphide ratio, oxidised low-density lipoprotein and F2α-isoprostanes [F2-Isop]), inflammation markers (myeloperoxidase and C-reactive protein [CRP]) and skeletal muscle damage markers (lactate dehydrogenase and creatine kinase [CK]). RESULTS: Our results showed that F2-Isop, CRP and CK levels significantly increased at T1 only in the PLA group (p < 0.05, p < 0.05 and p < 0.001, respectively) with no change in the SPI group, which reflects the effect of spirulina to prevent lipid peroxidation, inflammation and skeletal muscle damage induced by exhaustive exercise. Moreover, spirulina supplementation accelerated the return to baseline values given that F2-Isop, CRP and CK levels at T2 were significantly lower than at T0 in the SPI group (p < 0.05, p < 0.01 and p < 0.001, respectively). CONCLUSIONS: Based on the markers used in the present study, our results show that spirulina supplementation potentially prevents exercise-induced lipid peroxidation, inflammation and skeletal muscle damage, and may also accelerate the recovery of some of these markers. Based on our findings, we recommend spirulina supplementation especially for those athletes who do not achieve the recommended antioxidant dietary intake and who perform a high training load aiming to reduce the magnitude of OS, inflammation and skeletal muscle damage, which could help to reduce performance losses and accelerate recovery after training/competitions throughout the season

Polyphenol-Rich Blackcurrant Juice Prevents Endothelial Dysfunction in the Mesenteric Artery of Cirrhotic Rats with Portal Hypertension: Role of Oxidative Stress and the Angiotensin System

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