Part II: beneficial effects of the peroxynitrite decomposition catalyst FP15 in murine models of arthritis and colitis
Details
Serval ID
serval:BIB_947E1A01A882
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Part II: beneficial effects of the peroxynitrite decomposition catalyst FP15 in murine models of arthritis and colitis
Journal
Molecular Medicine
ISSN
1076-1551 (Print)
Publication state
Published
Issued date
10/2002
Volume
8
Number
10
Pages
581-90
Notes
Journal Article
Research Support, U.S. Gov't, P.H.S. --- Old month value: Oct
Research Support, U.S. Gov't, P.H.S. --- Old month value: Oct
Abstract
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.
Keywords
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
Create date
24/01/2008 17:00
Last modification date
20/08/2019 14:57