Considering potential Tempol effects on
mdx
muscle fibers, in this study we evaluated its effects on relevant dystrophic phenotypic characteristics, such as muscle degeneration, inflammatory process and angiogenesis, which as yet have not been investigated.
Mdx
mice were randomly assigned into three groups:
mdxS
, the control group receiving intraperitoneal (i.p.) injections of saline solution (100μL);
mdxP
, positive control group receiving prednisolone (1mg/kg) by oral gavage; and
mdx
T, treated group receiving i.p. injections of tempol (100 mg/kg). C57BL/10 mice were also used as controls. Tempol treatment promoted gain in muscle strength and reduced myonecrosis and inflammatory response in the dystrophic diaphragm (DIA) and biceps brachii (BB) muscles. No evidence of Tempol's beneficial performance on angiogenesis in DIA and BB
mdx
muscles was found. The findings presented here show that Tempol treatment improves dystrophic phenotype, supporting its use as a potential therapeutic strategy in DMD.
Several studies have demonstrated that oxidative stress plays a critical function in the pathogenesis of Duchenne muscular dystrophy (DMD). 1-3 DMD is the most frequent and lethal muscular dystrophy, affecting 1 in 3000-6000 male children, 3 and at present, there is no efficient therapy for this dystrophy. 4 Mitochondria are one of the main sources of reactive oxygen species (ROS). Hydroxyl radical, superoxide anion, hydrogen peroxide and singlet oxygen constitute the ROS, and when produced in excess or not properly controlled, it becomes toxic. 5,6 There is feed-forward looping; the high levels of ROS produced by the mitochondrial electron transport chain damage the mitochondria and consequently lead to even greater production of ROS and mitochondrial injury. 6
This study aimed to investigate the effects of interval and continuous training on the body mass gain and adiposity levels of rats fed a high-fat diet. Forty-eight male Sprague-Dawley rats were randomly divided into two groups, standard diet and high-fat diet, and received their respective diets for a period of four weeks without exercise stimuli. After this period, the animals were randomly divided into six groups (n = 8): control standard diet (CS), control high-fat diet (CH), continuous training standard diet (CTS), continuous training high-fat diet (CTH), interval training standard diet (ITS), and interval training high-fat diet (ITH). The interval and continuous training consisted of a swimming exercise performed over eight weeks. CH rats had greater body mass gain, sum of adipose tissues mass, and lower serum high density lipoprotein values than CS. The trained groups showed lower values of feed intake, caloric intake, body mass gain, and adiposity levels compared with the CH group. No significant differences were observed between the trained groups (CTS versus ITS and CTH versus ITH) on body mass gains and adiposity levels. In conclusion, both training methodologies were shown to be effective in controlling body mass gain and adiposity levels in high-fat diet fed rats.
The mdx mouse phenotype aggravated by chronic exercise on a treadmill makes this murine model more reliable for the study of muscular dystrophy. Thus, to better assess the Tempol effect on dystrophic pathways, the analyses in this study were performed in the blood samples and diaphragm muscle from treadmill trained adult (7–11-weeks old) mdx animals. The mdx mice were divided into three groups: mdxSed, sedentary controls (n = 28); mdxEx, exercise-trained animals (n = 28); and mdxEx+T, exercise-trained animals with the Tempol treatment (n = 28). The results demonstrated that the Tempol treatment promoted muscle strength gain, prevented muscle damage, reduced the inflammatory process, oxidative stress, and angiogenesis regulator, and up regulated the activators of mitochondrial biogenesis. The main new findings of this study are that Tempol reduced the NF-κB and increased the PGC1-α and PPARδ levels in the exercise-trained-mdx mice, which are probably related to the ability of this antioxidant to scavenge excessive ROS. These results reinforce the use of Tempol as a potential therapeutic strategy in DMD.
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