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Figure 1.

Allopurinol prevents soleus muscle atrophy after 14 days of hindlimb unloading in rats.

(A) The reticulin staining (Original magnification, 4×) shows a significant decrease in the soleus muscle cross-sectional area after hindlimb unloading. Allopurinol partially prevents it (Scale bar, 1 mm). (B) Quantitative analyses were used to confirm histological findings, by comparing the cross-sectional area of the different groups: control rats with water (CW) (n = 3), control rats with allopurinol (CA) (n = 3), unloading rats with water (UW) (n = 3) and unloading rats with allopurinol (UA) (n = 3). (C) Soleus muscle to body mass ratio. Values are mean (±SD) in CW (n = 9), CA (n = 9), UW (n = 7), and UA (n = 7). (D) Western blot and densitometric analysis of slow skeletal muscle myosin heavy chain in CW (n = 3), CA (n = 3), UW (n = 3), and UA (n = 3). A two-factor ANOVA and post hoc Bonferroni's comparisons were used to identify significant differences.

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Figure 1 Expand

Figure 2.

Hindlimb unloading activates plasma and soleus muscle XO. Prevention by allopurinol.

Mean (±SD) results of XO activity in plasma (A) and soleus (B) of control with water (CW) (n = 9), control with allopurinol (CA) (n = 9), unloaded with water (UW) (n = 7) and unloaded with allopurinol (UA) (n = 7) rats. A two-factor ANOVA and post hoc Bonferroni's comparisons were used to identify significant differences.

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Figure 3.

Effect of unloading and allopurinol treatment on soleus muscle and plasma protein carbonylation.

Mean (±SD) results of soleus muscle carbonylated proteins (A) of control with water (CW) (n = 9), control with allopurinol (CA) (n = 9), unloaded with water (UW) (n = 7) and unloaded with allopurinol (UA) (n = 7) rats. Figure B represents carbonylation of low-molecular weight protein (less than 50 kDa) in plasma of the same animals. A two-factor ANOVA and post hoc Bonferroni's comparisons were used to identify significant differences.

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Figure 4.

Effect of unloading and allopurinol treatment on the protein levels of soleus muscle antioxidant enzymes.

Mean (±SD) results of CuZnSOD (A) and Catalase (B) protein levels in soleus muscle of control with water (CW) (n = 9), control with allopurinol (CA) (n = 9), unloaded with water (UW) (n = 7) and unloaded with allopurinol (UA) (n = 7) rats. A two-factor ANOVA and post hoc Bonferroni's comparisons were used to identify significant differences.

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Figure 5.

Effect of unloading and allopurinol treatment on the activation of p38 MAPK.

Mean (±SD) results of cytosolic p38 MAPK in soleus muscle of control with water (CW) (n = 9), control with allopurinol (CA) (n = 9), unloaded with water (UW) (n = 7) and unloaded with allopurinol (UA) (n = 7) rats. Activation levels were expressed as the ratio between phosphorylated and total protein content. A two-factor ANOVA and post hoc Bonferroni's comparisons were used to identify significant differences.

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Figure 6.

Effect of unloading and allopurinol treatment on the MAFbx levels in soleus muscle.

Mean (±SD) results of MAFbx mRNA levels in soleus muscle of control with water (CW) (n = 9), control with allopurinol (CA) (n = 9), unloaded with water (UW) (n = 7) and unloaded with allopurinol (UA) (n = 7) rats. A two-factor ANOVA and post hoc Bonferroni's comparisons were used to identify significant differences.

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Figure 6 Expand

Figure 7.

Allopurinol prevents the loss of muscle mass during hindlimb unloading via inhibition of p38 MAPK and the E3 ubiquitin ligase Atrogin1/MAFbx.

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Figure 7 Expand

Table 1.

Primer sequences used for real-time PCR.

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Table 1 Expand