Malondialdehyde (MDA) was the sole means used to measure oxidative stress in this
3. Szabo, Csaba; Liaudet, Lucas; Mabley, Jon G.; Pacher, Pal;
Salzman, Andrew L.; Southan, Garry J.
JOURNAL NAME- Molecular Medicine (Baltimore) VOL. 8 NO. 10 October 2002 2002 PP. 581-590.
DOCUMENT TYPE- Article ISSN- 1076-1551
ADDRESS- Inotek Pharmaceuticals, Suite 419E , 100 Cummings Center, Beverly , MA , 01915 , USA ,
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.
Return from Free Radical Reference 3 Malondialdehyde
to Free Radical Laboratory Validation 1.