Desferrioxamine suppresses experimental allergic encephalomyelitis induced by MBP in SJL mice.

Pedchenko TV, LeVine SM
J Neuroimmunol. 1998 84 (2): 188-97

PMID: 9628462 · DOI:10.1016/s0165-5728(97)00256-7

Data from several studies indicate that free radicals have a pathogenic role in experimental allergic encephalomyelitis (EAE). Iron can contribute to free radical damage by catalyzing the formation of hydroxyl radical, inducing secondary initiation of lipid peroxidation and by promoting the oxidation of proteins. The iron chelator, desferrioxamine, can limit these oxidative reactions and it can scavenge peroxynitrite independent of iron chelation. Two previous studies have examined the therapeutic value of desferrioxamine in EAE. One study observed an effect when disease was induced by spinal cord homogenates (J. Exp. Med. 160, p. 1532, 1984), but a second study found no therapeutic value of desferrioxamine for myelin basic protein (MBP)-induced EAE (J. Neuroimmunol. 17, p. 127, 1988). In the second study, the drug was only administered during the preclinical stages of disease. Since desferrioxamine scavenges free radicals and prevents their formation, we hypothesized that the drug should be given during the active stage of disease to have therapeutic value. We first demonstrated that the drug enters the CNS around inflammatory cells in EAE animals. In animals treated during the active stage of MBP-induced EAE, the clinical signs were significantly reduced compared to vehicle-treated animals. The iron-bound form of this drug, ferrioxamine, was without therapeutic value. A derivative of desferrioxamine, hydroxylethyl starch (HES)-desferrioxamine, has a greater plasma half-life than desferrioxamine and it was also tested. Although there was a suggestion of improvement in these animals, the effects were less than that observed for desferrioxamine which may be related to the greater molecular size of HES-desferrioxamine. In summary, these data suggest that chelation of iron is an effective therapeutic target for EAE.

MeSH Terms (16)

Animals Deferoxamine Demyelinating Diseases Encephalomyelitis, Autoimmune, Experimental Ferric Compounds Free Radicals Hydroxyethyl Starch Derivatives Immunohistochemistry Iron Iron Chelating Agents Male Mice Mice, Inbred Strains Myelin Basic Protein Myelin Sheath Tissue Distribution

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