Allopurinol mitigates muscle contractile dysfunction caused by hindlimb unloading in mice

Area of Science:

• Skeletal Muscle Physiology
• Spaceflight and Bed Rest Research
• Pharmacology

Background:

• Prolonged mechanical unloading causes skeletal muscle weakness, a significant issue in spaceflight and bed rest.
• Antioxidants show potential in mitigating muscle weakness from immobilization.
• Allopurinol, a xanthine oxidase inhibitor with antioxidant properties, was investigated for its protective effects on unloaded muscles.

Purpose of the Study:

• To evaluate the efficacy of allopurinol in preventing functional decline in unloaded antigravity muscles.
• To determine if allopurinol can protect soleus muscle function against hindlimb suspension-induced weakness.

Main Methods:

• Adult mice underwent 12 days of hindlimb suspension, with or without allopurinol administration.
• Control groups included freely ambulating mice.
• Soleus muscles were isolated for ex vivo functional and biochemical analyses.

Main Results:

• Unloading significantly decreased soleus muscle weight, cross-sectional area, and tetanic force, while increasing oxidant activity and passive compliance.
• Allopurinol partially inhibited the loss of absolute force and force/area in unloaded muscles.
• Allopurinol did not prevent muscle atrophy but did mitigate changes in passive muscle compliance.

Conclusions:

• Allopurinol does not inhibit skeletal muscle atrophy due to unloading.
• Allopurinol lessens the contractile dysfunction associated with prolonged unloading.
• These findings suggest a potential therapeutic benefit of allopurinol for individuals experiencing muscle weakness due to unloading.