One of the risks associated with long-duration space missions is decreased skeletal muscle function. Lack of weight-bearing activity in microgravity leads to loss of muscle mass and problems with muscle contractions. In select situations like extravehicular activity, muscle fatigue could limit performance. When muscles do not bear weight, a loss of oxidant regulation occurs that contributes to atrophy and decreased function. In this study, Dr. Michael B. Reid seeks to define the loss of oxidant regulation and determine the time course, composition and the source of increased oxidant activity in non weight-bearing muscle. He will then evaluate selected antioxidants for their success in neutralizing and/or preventing muscle weakness and fatigue.
Redox Modulation of Skeletal Muscle Function in Microgravity
Michael B. Reid, Ph.D.
University of Kentucky Medical Center
- To determine the time course, composition and source of increased oxidant activity in unloaded muscle. Experiments used mice conditioned by hindlimb unloading for up to two weeks. The antigravity muscle soleus was studied to define the time course of oxidant dysregulation after unloading, to determine the relative contributions of reactive oxygen species versus nitric oxide derivatives, and to test mitochondria as the primary source of increased oxidant activity.
- To evaluate selected antioxidants as countermeasures for weakness in unloaded muscle. In these experiments, mice conditioned by hindlimb unloading were treated with one of four interventions that oppose oxidant activity or oxidant-mediated signaling: allopurinol (xanthine oxidase inhibitor), curcumin (NF-kappaB inhibitor), Bowman-Birk inhibitor complex (protease inhibitor), or N-acetylcysteine (NAC; reduced thiol donor). Unloaded soleus was tested for protection against oxidative stress, contractile dysfunction and muscle atrophy.
- To test NAC as a countermeasure for handgrip fatigue in humans. Experiments in healthy volunteers defined the appropriate preparation (solution versus capsule) and dosage for oral NAC administration and tested NAC effects on handgrip strength and handgrip fatigue during concentric exercise.
The second problem is familiar to us all. Acute muscle fatigue is a common feature of strenuous exercise. A countermeasure to inhibit fatigue would benefit a broad range of the U.S. populace whose work requires physical exertion ranging from military professionals and firefighters, to police officers and construction workers. The implications for professional athletes are all too obvious.