Reduction of free radicals in multiple sclerosis: effect of glatiramer acetate (Copaxone).
Free radicals have been found in high concentrations within inflammatory multiple sclerosis (MS) lesions. The superoxide anion (O(2)(-)) reacts rapidly with nitric oxide (NO), producing peroxynitrite (ONOO(-)). Glatiramer acetate (GA) is a specific MS immunomodulator that induces the synthesis of Th2 cytokines, and reduces the frequency of relapses and the formation of active brain lesions. Proinflammatory cytokines could play a role in free radicals production in the peripheral immune system as well as in the central nervous system (CNS). The effect of GA on iNOS, superoxide radicals (O(2)(-)) and 3-nitrotyrosine production by peripheral blood adherent mononuclear cells (PBAMs) was assessed. Our findings demonstrate that in vitro GA reduced spontaneous and LPS-induced iNOS, 3-nitrotyrosine, NO and O(2)(-) production, and that similar inhibition can be demonstrated ex vivo in mononuclear cells obtained from GA-treated patients. The inhibition of the production of free radicals in PBAMs may represent a new therapeutic mechanism against inflammation during MS.
Iarlori
C
C
Department of Oncology and Neuroscience, University G. D'Annunzio, Chieti, Italy.
Gambi
D
D
Lugaresi
A
A
Patruno
A
A
Felaco
M
M
Salvatore
M
M
Speranza
L
L
Reale
M
M
D000328:Adult; D002478:Cells, Cultured; D005260:Female; D005609:Free Radicals / Q000378:metabolism*; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000378:metabolism*; D009569:Nitric Oxide / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010455:Peptides / Q000008:administration & dosage*; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D005609:Free Radicals; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D010455:Peptides; D013481:Superoxides; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D000068717:Glatiramer Acetate; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II