Oxidative Stress - Chronic Obstructive Pulmonary Disease - page 296

andplasma antioxidant capacity (12). Thus there is clear evidence that oxidants
in cigarette smoke markedly decrease plasma antioxidants.
Studies showing depletion of total antioxidant capacity in smokers are
associated with depletion of the major plasma antioxidants, i.e., ascorbic
acid, vitamin E, b -carotene, and selenium in the serum of chronic smokers
(42). Moreover, decreased vitamin E and vitamin C levels were reported
in leukocytes from smokers (1). Ascorbate appears to be a particularly
important antioxidant in the plasma (Table 3). Cigarette smoke-induced
lipid peroxidation of plasma in vitro is decreased by ascorbate (1). These
studies have suggested that cigarette smoking depletes a variety of multiple
antioxidants that are needed to quench an array of free radicals present in
cigarette smoke and to inhibit the inflammatory response induced by cigar-
ette smoking. Changes in other antioxidants and antioxidant enzymes in
response to cigarette smoke have been variable. Reduced levels of vitamin
E in the BAL fluid of smokers and a marginal increase in vitamin C in
BALF of smokers, compared to non-smokers, have been shown (1). Simi-
larly, alveolar macrophages from smokers have both increased levels of
ascorbic acid and augmented uptake of ascorbate (1). Increased activity of
antioxidant enzymes (SOD and catalase) in alveolar macrophages from
young smokers has also been reported (1). However, increased superoxide
generation by alveolar macrophages in elderly smokers was associated with
decreased antioxidant enzyme activities when compared with non-smokers.
The activities of CuZnSOD, glutathione-S-transferase (GST), and
glutathione peroxidase (GP) are all decreased in alveolar macrophages from
elderly smokers. These direct and indirect studies indicate that an increased
systemic and local pulmonary oxidant burden occurs in smokers, and in
patients with COPD (1).
X. DEPLETION OF LUNG GLUTATHIONE
Several studies have suggested that GSH homeostasis may play a central
role in the maintenance of the integrity of the lung airspace epithelial
barrier. Decreasing the levels of GSH in epithelial cells leads to loss of
barrier function and increased permeability (14,43,44).
There is limited information on the respiratory epithelial antioxidant
defenses in smokers, and less for patients with COPD. Several studies have
shown that GSH is elevated in BALF in chronic smokers (14,45). However,
this increase is not present immediately after acute cigarette smoking (14).
However, Harju et al. (46) have found that the g -glutamylcysteine
synthetase, g -GCS (now called as g -glutamylcysteine ligase) immunoreactivity
was decreased (GSH levels were not measured) in the airways of smokers
compared to non-smokers suggesting that cigarette smoke predisposes lung
cells to ongoing oxidant stress. This suggests the twofold increase in BALF