Low intensity training improves redox status and reduces collagen fibers on dystrophic muscle

Abstract

Exercise therapy on skeletal muscle of muscular dystrophies has no defined parameters. The effect of low-intensity treadmill training on the oxidative stress markers and fibrosis on hindlimb muscles was investigated. Sixteen dystrophic male mdx animals were separated in trained ( mdx T/n=8) and untrained ( mdx NT/n=8) groups. Wild type animals (WT/n=8) were used as healthy control. The mdx T group runned at a horizontal treadmill (9 m/min, 30 min/day, 3 times/wk, 8 weeks). Gastrocnemius and tibial anterior muscles were collected for analysis of enzymatic/non-enzymatic oxidant activity, oxidative damage concentration, collagen fibers area morphometry. The mdx T group presented a lower collagen fiber area compared to mdx NT for gastrocnemius ( P =0.025) and tibial anterior ( P =0.000). Oxidative damage activity was higher in the mdx T group for both muscles compared to mdx NT. Catalase presented similar activity for tibial anterior ( P =0.527) or gastrocnemius ( P =0.323). Superoxide dismutase ( P =0.003) and total antioxidant capacity ( P =0.024) showed increased activity in the mdx T group at tibial anterior with no difference for gastrocnemius. Low-intensity training is considered therapeutic as it reduces collagen deposition while improving tissue redox status.

Exercise-Related Oxidative Stress as Mechanism to Fight Physical Dysfunction in Neuromuscular Disorders

“…In fact, a voluntary swimming training for 30 min, 4 days/week for 4 weeks, improved the expression of proteins involved in energy metabolism and in muscle contraction, as well as decreased oxidized proteins (Hyzewicz et al, 2015). Low-intensity treadmill training (9 m/min, 30 min/day, three times/week, for 8 weeks) reduced collagen deposition, enhancing both enzymatic and total antioxidant capacity (Fernandes et al, 2019).…”

Beneficial Role of Exercise in the Modulation of mdx Muscle Plastic Remodeling and Oxidative Stress

“…Several studies have shown that treadmill exercise can efficiently modulate this process. Indeed, a low intensity exercise, at a speed of 9 m/min for two months, on a horizontal platform reduces collagen deposition in limb muscles of mdx mice [ 73 , 74 , 75 ]. In addition, low intensity running induced a strong beneficial effect on the degeneration-regeneration process of mdx muscle and a shift in favor of regeneration, both in limb muscles and in diaphragm [ 76 , 77 ], and reduced the percentage of necrotic area in mdx soleus and gastrocnemius muscles, while it seemed to exert opposite effects on mdx plantaris muscle [ 78 ].…”

“…Based on the above reported experimental evidences, we can conclude that beneficial effects on mdx limb muscles induced by horizontal treadmill running exercise depend primarily on training intensity, being mainly associated to running speed ranging between 4 and 9 m/min. These positive effects, including fibrosis reduction, increased regeneration, improvement of muscle performances and structure, such as muscle hypertrophy and fiber type switch, seem to be not influenced by age, since they can be found in mdx mice 4–5 weeks old [ 108 , 109 ], 8 weeks old [ 74 , 76 , 77 , 110 ], and up to 20 weeks old [ 73 , 75 , 79 ], or by the duration of training, given the persistence of positive effects for exercise duration ranging between 1 and 6 months. On the contrary, horizontal treadmill exercise at higher intensity, with speed equal or greater than 12 m/min, or downhill/uphill running, generally exert detrimental effects on mdx muscles, and are often used to worsen the mdx phenotype before assessing the efficacy of drug treatment [ 8 , 81 , 82 , 84 , 87 , 92 , 99 ].…”

“…8 weeks of low intensity treadmill running, at a speed of 9 m/min, started when mice were 4 weeks old, reversed lipid and protein oxidation in the gastrocnemius of mdx mice [ 108 , 109 ], increased the antioxidant activity of glutathione, free thiols concentrations and reversed the changes in mitochondrial respiratory chain complex activity associated to the disease, thus improving energy metabolism [ 108 ]. The same exercise protocol, started when mice were 11 weeks old, although associated with higher levels of lipid peroxidation and protein carbonylation in the tibial anterior and gastrocnemius muscles, was also able to enhance SOD activity and total antioxidant capacity [ 73 ]. These observations suggest that the exercise-dependent increase in antioxidant enzymes is not sufficient to reverse oxidative damage to macromolecules, likely due to the age of treatment initiation, but can sustain the attenuation of intramuscular collagen fibers deposition [ 73 ], which occurs in mdx mice after the tenth week of age [ 8 ].…”

“…The same exercise protocol, started when mice were 11 weeks old, although associated with higher levels of lipid peroxidation and protein carbonylation in the tibial anterior and gastrocnemius muscles, was also able to enhance SOD activity and total antioxidant capacity [ 73 ]. These observations suggest that the exercise-dependent increase in antioxidant enzymes is not sufficient to reverse oxidative damage to macromolecules, likely due to the age of treatment initiation, but can sustain the attenuation of intramuscular collagen fibers deposition [ 73 ], which occurs in mdx mice after the tenth week of age [ 8 ]. A modulation of antioxidant defenses was also observed following 30 days of low intensity endurance exercise on rotating treadmill, which produced an increase in quadriceps SOD1 levels [ 110 ].…”