EUK‐134, a synthetic superoxide dismutase/catalase mimetic, protects against loss of muscle mass/body mass in diaphragm and gastrocnemius in mdx mice

Abstract

Duchenne muscular dystrophy (DMD) is characterized by devastating muscle degeneration associated with oxidative stress, loss of contractile tissue, muscle atrophy, muscle weakness and increased fibrosis in respiratory and locomotor muscles. We tested the hypothesis that protection against oxidative stress via the catalase/superoxide dismutase mimetic EUK‐134 will prevent reduction of diaphragm and skeletal muscle mass/body mass during the early inflammatory phase (20‐28 days) in mdx mice. C57BL(wild type) and mdx mice were given EUK‐134 (30mg/kg body weight/day, i.p., injection) for 8 days, beginning at 20 days of age. Body mass was significantly lower in mdx mice (‐37.7%) than wild type but, EUK‐134 increased body mass by 15.5% in mdx mice. Absolute muscle mass was lower in diaphragm (‐44.3%), gastrocnemius (‐53.6%), tibialis anterior (‐58.1%) in mdx mice. Muscle mass/body mass was lower in diaphragm (‐11.4%), gastrocnemius (‐26.3%), tibialis anterior (‐34.4%), but not heart, plantaris, soleus, extensor digitorum longus in mdx mice. EUK‐134 had a significant positive effect in protecting against reduced muscle mass/body mass in diaphragm (+38.7%) and gastrocnemius (+27.1%) in mdx mice. These data indicate that EUK‐134 provide protection against reduced muscle mass/body mass in diaphragm and gastrocnemius in mdx mice during this early phase of muscular dystrophy. Supported by NIH Grant (AR054084).