LAZAROIDS ENHANCE SKELETAL MYOGENESIS IN PRIMARY CULTURES OF DYSTROPHIN-DEFICIENT MDX MICE

Growing evidence suggests a role for free radicals in the degeneration of dystrophin-deficient muscle (as observed in Duchenne muscular dyst rophy). We therefore decided to test the action of the lazaroid antiox idant compounds on primary skeletal muscle cell cultures derived from an animal model of Duchenne muscular dystrophy, the mdx mouse. Both vi tamin E-derived U-83836E and glucocorticoid-derived U-74389F enhanced myogenesis of dystrophin-deficient cultures as determined by the numbe r of myotubes, the amount of nicotinic acetylcholine receptor, skeleta l muscle alpha-actin levels and myosin light chain. U-83836E enhanced myogenesis of control congenic C57BL/10 mouse-derived muscle cultures whereas U-74389F had no detectable effect. This enhanced myogenesis wa s in most respects similar to the one triggered by alpha-methylprednis olone which is the only drug known to be beneficial in Duchenne muscul ar dystrophy.