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 dystrophy). We therefore decided to test the action of the lazaroid antioxidant compounds on primary skeletal muscle cell cultures derived from an animal model of Duchenne muscular dystrophy, the mdx mouse. Both vitamin E-derived U-83836E and glucocorticoid-derived U-74389F enhanced myogenesis of dystrophin-deficient cultures as determined by the number of myotubes, the amount of nicotinic acetylcholine receptor, skeletal 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 was in most respects similar to the one triggered by alpha-methylprednisolone which is the only drug known to be beneficial in Duchenne muscular dystrophy.
Metzinger
L
L
Laboratoire de Biologie et Pharmacologie Neuromusculaires, Université Louis Pasteur (ULP), Illkirch, France.
Passaquin
A C
AC
Vernier
A
A
Thiriet
N
N
Warter
J M
JM
Poindron
P
P
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004347:Drug Interactions; D016189:Dystrophin / Q000172:deficiency*; D008775:Methylprednisolone / Q000494:pharmacology; D051379:Mice; D018101:Mice, Inbred mdx; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development*; D010879:Piperazines / Q000494:pharmacology*; D011281:Pregnatrienes / Q000494:pharmacology*; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D002839:Chromans; D003598:Cytoskeletal Proteins; D016189:Dystrophin; D010879:Piperazines; D011281:Pregnatrienes; D011950:Receptors, Cholinergic; C074965:U 74389F; C066382:U 78517F; D008775:Methylprednisolone