A catalyst of peroxynitrite decomposition inhibits murine experimental autoimmune encephalomyelitis

J Neuroimmunol. 2000 Jul 10;107(1):21-8. doi: 10.1016/s0165-5728(00)00242-3.


Peroxynitrite (PN), the product of nitric oxide (NO) reacted with superoxide, is generated at sites of inflammation. Nitrotyrosine (NT), a marker of PN formation, is abundant in lesions of acute experimental autoimmune encephalomyelitis (EAE), and in active multiple sclerosis (MS) plaques. To determine whether PN plays a role in EAE pathogenesis, mice induced to develop EAE were treated with a catalyst specific for the decomposition of PN. Because this catalyst has no effect upon NO, using it allowed differentiation of PN-mediated effects from NO-mediated effects. Mice receiving the PN decomposition catalyst displayed less severe clinical disease, and less inflammation and demyelination than control mice. Encephalitogenic T cells could be recovered from catalyst-treated mice, indicating that the PN decomposition catalyst blocked the pathogenic action of PN at the effector stage of EAE, but was not directly toxic to encephalitogenic T cells. PN plays an important role distinct from that of NO in the pathogenesis of EAE, a major model for MS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Catalysis
  • Central Nervous System / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control*
  • Female
  • Ferric Compounds / pharmacology*
  • Immunohistochemistry
  • Lymphocyte Transfusion
  • Lymphocytes / immunology
  • Metalloporphyrins / pharmacology*
  • Mice
  • Mice, Inbred Strains
  • Nitrates / metabolism*
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism


  • 5,10,15,20-tetrakis(2,4,6-trimethyl-3,3-disulfonatophenyl)porphyrinato iron(III)
  • Ferric Compounds
  • Metalloporphyrins
  • Nitrates
  • peroxynitric acid
  • 3-nitrotyrosine
  • Tyrosine
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse