Effect of mercaptoethylguanidine scavengers of peroxynitrite on the development of experimental allergic encephalomyelitis in PLSJL mice.
Peroxynitrite has been implicated in the pathogenesis of multiple sclerosis and its animal counterpart experimental allergic encephalomyelitis (EAE). Here we have examined the effects of the novel peroxynitrite scavengers, mercaptoethylguanidine (MEG) and guanidinoethyldisulphide (GED), on the development of EAE. Both MEG and GED delayed EAE onset and decreased the number of animals displaying disease signs. However, when EAE developed, its severity was not significantly abrogated by drug administration. These results suggest that while MEG and GED protect against the induction phase of EAE, they do not prevent disease progression. This may be due to the inability of MEG and GED to efficiently scavenge peroxynitrite or result from their capacity to inhibit inducible nitric oxide synthase. Therefore, the development of more potent and selective scavengers of peroxynitrite is necessary for use in EAE.
Scott
G S
GS
Department of Microbiology and Immunology, Thomas Jefferson University, 1020 Locust Street, JAH 454, Philadelphia, PA 19107, USA. gwen.scott@mail.tju.edu
Kean
R B
RB
Southan
G J
GJ
Szabó
C
C
Hooper
D C
DC
D000818:Animals; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D051379:Mice; D008817:Mice, Mutant Strains; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism*
D004791:Enzyme Inhibitors; D006146:Guanidines; C014363:bis(2-guanidinoethyl)disulfide; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C100078:2-mercaptoethylguanidine