Duchenne muscular dystrophy progression induced by downhill running is accompanied by increased endomysial fibrosis and oxidative damage DNA in muscle of mdx mice.

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle necrosis. One of the major challenges for prescribing physical rehabilitation exercises for DMD patients is associated with the lack of a thorough knowledge of dystrophic muscle responsiveness to exercise. This study aims to understand the relationship between myogenic regulation, inflammation and oxidative stress parameters, and disease progression induced by downhill running in the skeletal muscle of an experimental model of DMD. Six-month-old C57BL/10 and C57BL/10-DMDmdx male mice were distributed into three groups: Control (C), mdx, and mdx + Exercise (mdx + Ex). Animals were trained in a downhill running protocol for seven weeks. The gastrocnemius muscle was subjected to histopathology, muscle regeneration (myoD and myogenin), inflammation (COX-2), oxidative stress (8-OHdG) immunohistochemistry markers, and gene expression (qPCR) of NF-kB and NADP(H)Oxidase 2 (NOX-2) analysis. In the mdx + Ex group, the gastrocnemius muscle showed a higher incidence of endomysial fibrosis and a lower myonecrosis percentage area. Immunohistochemical analysis revealed decreased myogenin immunoexpression in the mdx group, as well as accentuated immunoexpression of nuclear 8-OHdG in both mdx groups and increase in cytoplasmic 8-OHdG only in the mdx + Ex. COX-2 immunoexpression was related to areas of regeneration process and inflammatory infiltrate in the mdx group, while associated with areas of muscle fibrosis in the mdx + Ex. Moreover, the NF-kB gene expression was not influenced by exercise; however, a NAD(P)HOxidase 2 increase was observed. Oxidative stress and oxidative DNA damage play a significant role in the DMD phenotype progression induced by exercise, compromising cellular patterns resulting in increased endomysial fibrosis.

Paradoxical sleep deprivation induces tissue changes in the parotid gland of rats.

PURPOSE: This study aimed to evaluate if paradoxical sleep deprivation induces some tissue changes in the parotid gland of rats. METHODS: A total of 24 male Wistar rats were distributed into the following groups, as follows: Group 1-Control (CTRL; n = 8); Group 2-Sleep deprivation (PS; n = 8): the animals were submitted to Paradoxical Sleep deprivation for 96 h and Group 3-Recovery (R; n = 8): the animals were submitted to sleep loss for 96 h, followed by a period of 96 h without any intervention. The following parameters were evaluated: microscopic analysis, immunohistochemistry for Caspase-3, Ki-67, and COX-2 and gene expression of cytochrome C, TNF-α, and Interleukins 6, 10. RESULTS: The results pointed out acinar atrophy, and the presence of cytoplasmic vacuoles in the parenchyma of the experimental groups. In the same groups, there was differential expression of interleukins 6, 10 and TNF-α. Apoptosis was also increased by means of cleaved caspase 3 expression. The cellular proliferation (ki-67 expression) was increased the R group. CONCLUSION: Taken together, sleep deprivation induces tissue degeneration, inflammatory process, as well as activate apoptosis in the parotid gland of rats.

Inflammatory activity and apoptosis are associated with tissue degeneration in the submandibular gland of rats submitted to paradoxical sleep deprivation.

The aim of this study was to evaluate if paradoxical sleep deprivation is able to induce tissue degeneration, inflammatory activity and apoptosis in the submandibular gland of rats. A total of 24 male Wistar rats were distributed into the following groups: group 1-control (CTRL; n = 8): the animals were not submitted to any procedures; group 2-sleep deprivation (PS; n = 8): the animals were submitted to paradoxical sleep deprivation for 96 h and group 3-recovery (R; n = 8): the animals were submitted to sleep deprivation for 96 h, followed by a period of 96 h without any intervention. The following parameters were evaluated: histopathological analysis, immunohistochemistry for Ki-67, COX-2 and cleaved caspase-3 and gene expression of TNF-α, Interleukin 6 (IL-6), Interleukin 10 (IL-10) and cytochrome C by real-time PCR. The results pointed out cytoplasmic vacuoles and congested vessels in the parenchyma of submandibular gland the in PS and R groups. The expression of interleukins 6, 10 and TNF-ɑ was differentially expressed in the PS and R groups. Apoptosis was also triggered by means of increasing cleaved caspase-3 and cytochrome c expression. The cellular proliferation (Ki-67 index) was also positive in the R group. Taken together, our results demonstrate that sleep deprivation is capable of promoting tissue degeneration in the submandibular gland, as a result of inflammatory response and cellular death in rats.

Duchenne muscular dystrophy progression induced by downhill running is accompanied by increased endomysial fibrosis and oxidative damage DNA in muscle of mdx mice

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle necrosis. One of the major challenges for prescribing physical rehabilitation exercises for DMD patients is associated with the lack of a thorough knowledge of dystrophic muscle responsiveness to exercise. This study aims to understand the relationship between myogenic regulation, inflammation and oxidative stress parameters, and disease progression induced by downhill running in the skeletal muscle of an experimental model of DMD. Six-month-old C57BL/10 and C57BL/10-DMDmdx male mice were distributed into three groups: Control (C), mdx, and mdx + Exercise (mdx + Ex). Animals were trained in a downhill running protocol for seven weeks. The gastrocnemius muscle was subjected to histopathology, muscle regeneration (myoD and myogenin), inflammation (COX-2), oxidative stress (8-OHdG) immunohistochemistry markers, and gene expression (qPCR) of NF-kB and NADP(H)Oxidase 2 (NOX-2) analysis. In the mdx + Ex group, the gastrocnemius muscle showed a higher incidence of endomysial fibrosis and a lower myonecrosis percentage area. Immunohistochemical analysis revealed decreased myogenin immunoexpression in the mdx group, as well as accentuated immunoexpression of nuclear 8-OHdG in both mdx groups and increase in cytoplasmic 8-OHdG only in the mdx + Ex. COX-2 immunoexpression was related to areas of regeneration process and inflammatory infiltrate in the mdx group, while associated with areas of muscle fibrosis in the mdx + Ex. Moreover, the NF-kB gene expression was not influenced by exercise; however, a NAD(P)HOxidase 2 increase was observed. Oxidative stress and oxidative DNA damage play a significant role in the DMD phenotype progression induced by exercise, compromising cellular patterns resulting in increased endomysial fibrosis.