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Improvement of endurance of DMD animal model using natural polyphenols.

Sitzia C, Farini A, Colleoni F, Fortunato F, Razini P, Erratico S, Tavelli A, Fabrizi F, Belicchi M, Meregalli M, Comi G, Torrente Y - Biomed Res Int (2015)

Bottom Line: Different mechanisms were hypothesized such as reduced hydroxyl radicals, nuclear factor-κB deactivation, and NO protection from inactivation.We observed a reduction of muscle fibrosis deposition and myofiber necrosis together with an amelioration of vascularization.Our data confirmed that ProAbe-based diet may represent a strategy to coadjuvate the treatment of DMD.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio Cellule Staminali, Dipartimento di Patofisiologia e dei Trapianti, Universitá degli Studi di Milano, Fondazione IRCCS Cá Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Via Francesco Sforza 35, 20122 Milano, Italy.

ABSTRACT
Duchenne muscular dystrophy (DMD), the most common form of muscular dystrophy, is characterized by muscular wasting caused by dystrophin deficiency that ultimately ends in force reduction and premature death. In addition to primary genetic defect, several mechanisms contribute to DMD pathogenesis. Recently, antioxidant supplementation was shown to be effective in the treatment of multiple diseases including muscular dystrophy. Different mechanisms were hypothesized such as reduced hydroxyl radicals, nuclear factor-κB deactivation, and NO protection from inactivation. Following these promising evidences, we investigated the effect of the administration of a mix of dietary natural polyphenols (ProAbe) on dystrophic mdx mice in terms of muscular architecture and functionality. We observed a reduction of muscle fibrosis deposition and myofiber necrosis together with an amelioration of vascularization. More importantly, the recovery of the morphological features of dystrophic muscle leads to an improvement of the endurance of treated dystrophic mice. Our data confirmed that ProAbe-based diet may represent a strategy to coadjuvate the treatment of DMD.

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Related in: MedlinePlus

Endurance test. Histogram representing endurance test of treated mice. (a) Each symbol corresponds to a single animal performance; endurance test was repeated once per day for 30 days for each mouse. The average value corresponds to the total amount of time measured during the tests for 30 days. As demonstrated by the average number of hours run mdx-treated mice increased significantly their performance versus untreated mice, even if this value was far from that of C57Bl mice (a). (b) Graph showed relative motor capacity of mice (percentage normalized to baseline) at 4 different time points (each week for 30 days). (c) Graph showed the absolute value of T4 of graph in (b) (that is the average time to exhaustion at T4 (30 days)) that was higher in mdx treated mice related to untreated ones. Tetanic force of TA (d) and DIA (e) was performed in treated and untreated mdx mice.
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fig2: Endurance test. Histogram representing endurance test of treated mice. (a) Each symbol corresponds to a single animal performance; endurance test was repeated once per day for 30 days for each mouse. The average value corresponds to the total amount of time measured during the tests for 30 days. As demonstrated by the average number of hours run mdx-treated mice increased significantly their performance versus untreated mice, even if this value was far from that of C57Bl mice (a). (b) Graph showed relative motor capacity of mice (percentage normalized to baseline) at 4 different time points (each week for 30 days). (c) Graph showed the absolute value of T4 of graph in (b) (that is the average time to exhaustion at T4 (30 days)) that was higher in mdx treated mice related to untreated ones. Tetanic force of TA (d) and DIA (e) was performed in treated and untreated mdx mice.

Mentions: To verify whether a natural polyphenols diet could improve muscular functionality we first test the endurance of treated and untreated mdx mice (n = 10 per each group). In these experiments we found that ProAbe administration significantly increased the endurance ability of mdx mice after 4 weeks of treatment (total average hours run: mdx treated 3,656 ± 0,728 versus mdx untreated 1,844 ± 0,426; P = 0,0474) (Figure 2(a)). We measured the total motor capacity relative to baseline performance and we observed an increase of 30% at day 30 of treatment (Figure 2(b)). Dystrophic animals assessed at 30 days of treatment showed an increased tolerance to exercise as demonstrated by the time to exhaustion (mdx treated 14,33 ± 0,817 versus mdx untreated 11,02 ± 0,849; P = 0,0117) (Figure 2(c)). Furthermore, we calculated the tetanic force of TA and DIA of treated and untreated mdx (n = 5 per each group) and we found a minimum but not significant improvement of the values in treated mdx muscles (Figures 2(d) and 2(e)).


Improvement of endurance of DMD animal model using natural polyphenols.

Sitzia C, Farini A, Colleoni F, Fortunato F, Razini P, Erratico S, Tavelli A, Fabrizi F, Belicchi M, Meregalli M, Comi G, Torrente Y - Biomed Res Int (2015)

Endurance test. Histogram representing endurance test of treated mice. (a) Each symbol corresponds to a single animal performance; endurance test was repeated once per day for 30 days for each mouse. The average value corresponds to the total amount of time measured during the tests for 30 days. As demonstrated by the average number of hours run mdx-treated mice increased significantly their performance versus untreated mice, even if this value was far from that of C57Bl mice (a). (b) Graph showed relative motor capacity of mice (percentage normalized to baseline) at 4 different time points (each week for 30 days). (c) Graph showed the absolute value of T4 of graph in (b) (that is the average time to exhaustion at T4 (30 days)) that was higher in mdx treated mice related to untreated ones. Tetanic force of TA (d) and DIA (e) was performed in treated and untreated mdx mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4377377&req=5

fig2: Endurance test. Histogram representing endurance test of treated mice. (a) Each symbol corresponds to a single animal performance; endurance test was repeated once per day for 30 days for each mouse. The average value corresponds to the total amount of time measured during the tests for 30 days. As demonstrated by the average number of hours run mdx-treated mice increased significantly their performance versus untreated mice, even if this value was far from that of C57Bl mice (a). (b) Graph showed relative motor capacity of mice (percentage normalized to baseline) at 4 different time points (each week for 30 days). (c) Graph showed the absolute value of T4 of graph in (b) (that is the average time to exhaustion at T4 (30 days)) that was higher in mdx treated mice related to untreated ones. Tetanic force of TA (d) and DIA (e) was performed in treated and untreated mdx mice.
Mentions: To verify whether a natural polyphenols diet could improve muscular functionality we first test the endurance of treated and untreated mdx mice (n = 10 per each group). In these experiments we found that ProAbe administration significantly increased the endurance ability of mdx mice after 4 weeks of treatment (total average hours run: mdx treated 3,656 ± 0,728 versus mdx untreated 1,844 ± 0,426; P = 0,0474) (Figure 2(a)). We measured the total motor capacity relative to baseline performance and we observed an increase of 30% at day 30 of treatment (Figure 2(b)). Dystrophic animals assessed at 30 days of treatment showed an increased tolerance to exercise as demonstrated by the time to exhaustion (mdx treated 14,33 ± 0,817 versus mdx untreated 11,02 ± 0,849; P = 0,0117) (Figure 2(c)). Furthermore, we calculated the tetanic force of TA and DIA of treated and untreated mdx (n = 5 per each group) and we found a minimum but not significant improvement of the values in treated mdx muscles (Figures 2(d) and 2(e)).

Bottom Line: Different mechanisms were hypothesized such as reduced hydroxyl radicals, nuclear factor-κB deactivation, and NO protection from inactivation.We observed a reduction of muscle fibrosis deposition and myofiber necrosis together with an amelioration of vascularization.Our data confirmed that ProAbe-based diet may represent a strategy to coadjuvate the treatment of DMD.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio Cellule Staminali, Dipartimento di Patofisiologia e dei Trapianti, Universitá degli Studi di Milano, Fondazione IRCCS Cá Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Via Francesco Sforza 35, 20122 Milano, Italy.

ABSTRACT
Duchenne muscular dystrophy (DMD), the most common form of muscular dystrophy, is characterized by muscular wasting caused by dystrophin deficiency that ultimately ends in force reduction and premature death. In addition to primary genetic defect, several mechanisms contribute to DMD pathogenesis. Recently, antioxidant supplementation was shown to be effective in the treatment of multiple diseases including muscular dystrophy. Different mechanisms were hypothesized such as reduced hydroxyl radicals, nuclear factor-κB deactivation, and NO protection from inactivation. Following these promising evidences, we investigated the effect of the administration of a mix of dietary natural polyphenols (ProAbe) on dystrophic mdx mice in terms of muscular architecture and functionality. We observed a reduction of muscle fibrosis deposition and myofiber necrosis together with an amelioration of vascularization. More importantly, the recovery of the morphological features of dystrophic muscle leads to an improvement of the endurance of treated dystrophic mice. Our data confirmed that ProAbe-based diet may represent a strategy to coadjuvate the treatment of DMD.

Show MeSH
Related in: MedlinePlus