Short-term treatment with Uncaria tomentosa aggravates the injury phenotype in mdx mice

Introduction: Uncaria tomentosa (Willd. ex Roem. & Schult.) DC. (Rubiaceae) or UT is a medicinal plant with antiviral, antimutagenic, anti-inflammatory and antioxidant properties. Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by mutations in the dystrophin gene; this deficiency leads to sarcolemma instability, inflammation, muscle degeneration and fibrosis. Objective: Considering the importance of inflammation to dystrophy progression and the anti-inflammatory activity of UT, in the present study we evaluated whether oral administration of UT extract would ameliorate dystrophy in the mdx mice, a DMD model. Methods: Eight-week-old male mdx mice were submitted to 200 mg/kg body weight daily UT oral administration for 6 weeks. General histopathology was analysed, and muscle tumor necrosis factor α, transforming growth factor-ß, myostatin and osteopontin transcript levels were assessed. The ability of mice to sustain limb tension to oppose their gravitational force was measured. Data were analysed with the unpaired Student's t-test. Results: Morphologically, both untreated and UT-treated animals exhibited internalised nuclei, increased endomysial connective tissue and variations in muscle fibre diameters. Body weight and muscle strength were significantly reduced in the UT-treated animals. Blood creatine kinase was higher in UT-treated compared to untreated animals. In tibialis anterior, myostatin, transcript was more highly expressed in the UT-treated while in the diaphragm muscle, transforming growth factor-ß transcripts were less expressed in the UT-treated. Conclusion: While previous studies identified anti-inflammatory, antiproliferative and anticarcinogenic UT effects, the extract indicates worsening of dystrophic muscles phenotype after short-term treatment in mdx mice.

Lack of dystrophin influences muscle inflammation but not myogenic regulatory factors after eccentric exercise in mdx mice

Abstract Aim: To investigate the consequences of chronic eccentric exercise in histopathology, inflammatory, and myogenic regulatory factors response in gastrocnemius muscle of X-chromosome-linked muscular dystrophy (mdx) mice. Method: Male mdx and control mice (C57BL/10 lineage) were distributed in the following groups: Sedentary Control (SC), Trained Control (TC), Sedentary Mdx (S-Mdx), and Trained Mdx (T-Mdx). Trained animals were subjected to downhill running for 7 weeks. Gastrocnemius was submitted to histopathological analysis and immunoexpression of Cyclooxygenase-2 (COX-2) and myogenic regulatory factors (myoD and myogenin). Results: The exercise influenced inflammation response as demonstrated by the increased COX-2 immunoexpression in T-Mdx. Interestingly, Myogenic regulatory factors revealed that the lack of dystrophin has not been influenced myoD and the increase of myogenin occurred due to exercise and was not aggravated by the absence of dystrophin. Conclusion: In conclusion, an eccentric exercise in gastrocnemius of mdx mice was characterized by an intense inflammatory process without myogenic response. These findings suggest that special attention should be given to inflammatory aspects related to COX-2 associated with a decrease of myoD expression, as biomarkers in motor rehabilitation programs.

The Effect of L-Carnitine Supplementation on the Dystrophic Muscle and Exercise Tolerance of Muscular Dystrophy (mdx) Mice

BACKGROUND: Duchenne muscular dystrophy is an X-linked recessive disorder leading to death in the late teens or early twenties. There is no effective pharmacological therapy for now. L-carnitine (LCAR), a naturally occurring compound facilitating the transport of fatty acid into mitochondria for -oxidation, has been getting an attention for its antiapoptotic and osmoprotective effect. The aim of this study is to evaluate if LCAR administration reduces dystrophic progression and enhances exercise tolerance in dystrophin deficient (mdx) mice. METHODS: Mdx mice (n=5) and wild type mice (n=5), aged 3 weeks were treated with oral LCAR (75mg/kg/day) for 6 weeks. Five each mdx and wild type mice were recruited for their counter-control. The animals underwent a 30-minute run on a horizontal treadmill for evaluating their exercise endurance. After 6-week training, baseline and post exercise serum CK of each group were analyzed. We examined sarcolemma integrity and muscle histology after exercise. Immunofluorescent stain and Western blot analysis for dystrophin-dystroglycan complex were also performed. RESULTS: LCAR-treated mdx mice showed higher exercise tolerance and lower serum CK value compared with those of control mice. The area of Evans blue dye uptake in LCAR-treated mdx mice was much smaller than that of control mdx mice. There was no remarkable difference in dystrophin-dystroglycan complex expression between treated and control mdx mice. CONCLUSIONS: LCAR seems to enhance exercise tolerance and decrease the breakdown of sarcolemma during strenuous exercise. Our study suggests the possibility of adjunctive therapeutic use of L-carnitine to the patients with Duchenne muscular dystrophy.