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

• Published in: Molecules (Basel, Switzerland) Switzerland), 2020-07, Vol.25 (13), p.3057
• Main Authors: Chen, Chang-Mu, Chung, Min-Ni, Chiu, Chen-Yuan, Liu, Shing-Hwa, Lan, Kuo-Cheng
• Format: Article
• Language: English
• Subjects: Acute promyeloid leukemia; Animals; Arsenic; Arsenic - toxicity; Arsenic trioxide; Atrophy; Biocompatibility; Birth weight; Cross-sections; Denervation; Denervation - adverse effects; Diabetes; Drinking water; Durability; Endurance; Exposure; Food contamination & poisoning; Glucose; Glycerol; Infants; Insulin resistance; Kinases; Leukemia; Male; Mice; Morphology; Muscle Proteins - metabolism; Muscle, Skeletal - drug effects; Muscle, Skeletal - pathology; Muscles; Muscular Atrophy - chemically induced; Muscular Atrophy - metabolism; Muscular Atrophy - pathology; Muscular function; Musculoskeletal system; Neurotoxicity; Promyeloid leukemia; Protein expression; Proteins; Rotator cuff; Sciatic nerve; skeletal muscle; SKP Cullin F-Box Protein Ligases - metabolism
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25133057

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 (As O ) for therapy. The potential of As O 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 As O (0.05 and 0.5 ppm) in drinking water for 4 weeks. We found that both 0.05 and 0.5 ppm As O 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 As O 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.