Inorganic Arsenic Exposure Decreases Muscle Mass and Enhances Denervation-Induced Muscle Atrophy in Mice

Arsenic is a toxic metalloid. Infants with a low birth-weight have been observed in areas with high-level arsenic in drinking water ranging from 463 to 1025 μg/L. A distal muscular atrophy side effect has been observed in acute promyelocytic leukemia patients treated with arsenic trioxide (As₂O₃) for therapy. The potential of As₂O₃ on muscle atrophy remains to be clarified. In this study, the myoatrophic effect of arsenic was evaluated in normal mice and sciatic nerve denervated mice exposed with or without As₂O₃ (0.05 and 0.5 ppm) in drinking water for 4 weeks. We found that both 0.05 and 0.5 ppm As₂O₃ increased the fasting plasma glucose level; but only 0.5 ppm arsenic exposure significantly decreased muscle mass, muscle endurance, and cross-sectional area of muscle fibers, and increased muscle Atrogin-1 protein expression in the normal mice. Both 0.05 and 0.5 ppm As₂O₃ also significantly enhanced the inhibitory effects on muscle endurance, muscle mass, and cross-sectional area of muscle fibers, and increased the effect on muscle Atrogin-1 protein expression in the denervated mice. These in vivo results suggest that inorganic arsenic at doses relevant to humans may possess myoatrophic potential.

Keywords: arsenic; atrophy; denervation; skeletal muscle.