Malondialdehyde (MDA) was the
sole means used to measure oxidative stress in this
study.
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.
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Radical Reference 3 Malondialdehyde
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