Oxidative Stress - Chronic Obstructive Pulmonary Disease - page 315

animal models (123,124). It would be interesting to see whether similar
results can be obtained by ebselen in response to smoking in vivo.
F. Redox Sensor Molecules
There are other small redox molecules such as b -strand mimetic template
MOL-294 and PNRI-299 which have been shown to inhibit NF- k Band
AP-1-mediated transcription and blocks allergic airway inflammation in a
mouse asthma model (125). The mechanism of inhibition is based on the
reversible inhibition of redox sensor proteins (similar to redox effector fac-
tor-1). These redox compounds are novel and have been shown to reduce
airway eosinophil infiltration, muscus hypersecretion, edema, and cytokine
release in mouse asthma model. However, the use of these compounds
against cigarette smoke-induced oxidative stress and the release of
pro-inflammatory mediators have not been tested in vitro or in vivo.
G. Polyphenols
Curcumin (diferuloyulmethane) is a naturally occurring flavonoid (polyphe-
nol) present in the spice, turmeric, which has a long traditional use as a che-
motherapeutic agent for many diseases. Curcumin is an active principle of
the perennial herb Curcuma longa (commonly known turmeric). Turmeric
has a long traditional use in the Orient for many ailments, particularly as
an anti-inflammatory agent. Recent studies have reported that curcumin
inhibits NF- k B expression = activation, IL-8 release cycloxygenase (COX-
2), HO-1, and neutrophil recruitment in the lungs (126,127). Curcumin
has multiple properties to protect against cigarette smoke-mediated oxida-
tive stress (126). It acts as oxygen radical and hydroxyl radical scavenger
which are formed by cigarette smoke, increases antioxidant glutathione
levels by induction of g -GCS and as an anti-inflammatory agent through
inhibition of NF- k B and IL-8 release in lung cells. Resveratrol, a flavanoid
found in red wine, is an effective inhibitor of inflammatory cytokine release
from macrophages in COPD patients (128). This anti-inflammatory prop-
erty of resveratrol may be due to its ability to induce sirtuins, and the
HDAC activity (129). The molecular mechanisms of anti-inflammatory
properties of dietary polyphenols against cigarette smoke = oxidative stress
have not yet been studied.
IX. CONCLUSIONS
There is now considerable evidence for the increased generation of ROS in
COPD, which may be important in the pathogenesis of this condition. ROS
may be critical in amplifying the normal inflammatory response to cigarette
smoke = environmental oxidants (noxious agents), through the upregulation
of redox-sensitive transcription factors and hence pro-inflammatory gene
expression, but are also involved in the protective mechanisms against the