Part II: beneficial effects of the peroxynitrite decomposition catalyst FP15 in murine models of arthritis and colitis

Détails

ID Serval
serval:BIB_947E1A01A882
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Part II: beneficial effects of the peroxynitrite decomposition catalyst FP15 in murine models of arthritis and colitis
Périodique
Molecular Medicine
Auteur(s)
Mabley  J. G., Liaudet  L., Pacher  P., Southan  G. J., Groves  J. T., Salzman  A. L., Szabo  C.
ISSN
1076-1551 (Print)
Statut éditorial
Publié
Date de publication
10/2002
Volume
8
Numéro
10
Pages
581-90
Notes
Journal Article
Research Support, U.S. Gov't, P.H.S. --- Old month value: Oct
Résumé
BACKGROUND: Peroxynitrite is a reactive oxidant species produced from nitric oxide and superoxide, which has been indirectly implicated in the pathogenesis of many inflammatory conditions including arthritis and colitis. Here, using a novel peroxynitrite decomposition catalyst, FP15, we directly investigate the role of peroxynitrite in the pathogenesis of arthritis and colitis in rodent models. METHODS: Arthritis was induced in mice by intradermal collagen injection; incidence and severity of arthritis was monitored using a macroscopic scoring system. At the end of the experiment paws were taken for determination of neutrophil infiltration (myeloperoxidase [MPO] activity), oxidative stress (malondialdehyde [MDA] level), and cytokine/chemokine levels. Colitis was induced in mice by 5% dextran sodium sulfate (DSS) in their drinking water. Colitis symptoms were assessed 10 days later, the parameters determined included body weight, rectal bleeding, colon length, colonic MPO and MDA levels, and colon histologic damage. RESULTS: Treatment with FP15 significantly reduced the inflammation and oxidative stress in arthritis and colitis. FP15 reduced both the incidence and severity of arthritis in mice and this was associated with reduced paw MPO and MDA levels. Similarly, in colitis, FP15 reduced colon damage, and this was associated with reduced colon neutrophil infiltration and oxidative stress. CONCLUSIONS:The protective effect of FP15 suggests that peroxynitrite plays a significant pathogenetic role in arthritis and colitis in the currently employed rodent models. Further work is needed to determine whether neutralization of peroxynitrite also represents a promising strategy to treat human inflammatory diseases such as arthritis and colitis.
Mots-clé
Administration, Oral Animals Arthritis/*drug therapy/*metabolism/pathology Catalysis/drug effects Colitis/*drug therapy/*metabolism/pathology Colon/drug effects/pathology Disease Models, Animal Male Metalloporphyrins/administration & dosage/pharmacology/*therapeutic use Mice Peroxynitrous Acid/*metabolism Time Factors
Pubmed
Web of science
Création de la notice
24/01/2008 18:00
Dernière modification de la notice
03/03/2018 19:37
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