Part II

Beneficial effects of the peroxynitrite decomposition catalyst FP15 in murine models of arthritis and colitis

Jon G. Mabley, Lucas Liaudet, Pál Pacher, Garry J. Southan, Andrew L. Salzman, Csaba Szabo

Research output: Contribution to journalArticle

48 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)581-590
Number of pages10
JournalMolecular Medicine
Volume8
Issue number10
StatePublished - Oct 1 2002
Externally publishedYes

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Peroxynitrous Acid
Colitis
Arthritis
Colon
Malondialdehyde
Peroxidase
Oxidative Stress
Neutrophil Infiltration
Rodentia
Intradermal Injections
Dextran Sulfate
Incidence
Chemokines
Oxidants
Superoxides
Drinking Water
Nitric Oxide
Collagen
Body Weight
Hemorrhage

ASJC Scopus subject areas

  • Genetics

Cite this

Part II : Beneficial effects of the peroxynitrite decomposition catalyst FP15 in murine models of arthritis and colitis. / Mabley, Jon G.; Liaudet, Lucas; Pacher, Pál; Southan, Garry J.; Salzman, Andrew L.; Szabo, Csaba.

In: Molecular Medicine, Vol. 8, No. 10, 01.10.2002, p. 581-590.

Research output: Contribution to journalArticle

Mabley, JG, Liaudet, L, Pacher, P, Southan, GJ, Salzman, AL & Szabo, C 2002, 'Part II: Beneficial effects of the peroxynitrite decomposition catalyst FP15 in murine models of arthritis and colitis', Molecular Medicine, vol. 8, no. 10, pp. 581-590.
Mabley, Jon G. ; Liaudet, Lucas ; Pacher, Pál ; Southan, Garry J. ; Salzman, Andrew L. ; Szabo, Csaba. / Part II : Beneficial effects of the peroxynitrite decomposition catalyst FP15 in murine models of arthritis and colitis. In: Molecular Medicine. 2002 ; Vol. 8, No. 10. pp. 581-590.
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