Allopurinol mitigates muscle contractile dysfunction caused by hindlimb unloading in mice

INTRODUCTION: Prolonged mechanical unloading induces skeletal muscle weakness, a major problem following extended bed rest or spaceflight. Antioxidants are reported to partially inhibit the weakness caused by limb immobilization. The current study tested allopurinol, a xanthine oxidase inhibitor with antioxidant properties, for its capacity to protect the function of unloaded antigravity muscles.

METHODS: Adult mice conditioned by 12 d of hindlimb suspension, with or without allopurinol 50 mg x kg(-1) x d(-1), were compared with freely ambulating controls. Animals were anesthetized and soleus muscles were isolated for ex vivo analyses.

RESULTS: Relative to control muscles, unloading decreased soleus weight (-44%; p < 0.05) and cross-sectional area (-38%; p < 0.05), increased cytosolic oxidant activity (-46%; p < 0.01), decreased absolute tetanic force (e.g., -64% at 250 Hz; p < 0.001 ) and force/area (-35%; p < 0.01), and increased passive compliance of the unstimulated muscle (p < 0.05). Allopurinol administration blunted the effects of unloading, partially inhibiting losses of absolute force (p < 0.05) and force/area (p < 0.05) without affecting muscle atrophy. The drug also blunted compliance changes in the passive muscle (p < 0.05).

DISCUSSION: Allopurinol does not inhibit atrophy of skeletal muscle caused by prolonged unloading. However, allopurinol does lessen the contractile dysfunction caused by unloading, an action that may have potential benefit for astronauts and bedridden individuals.