Biomedical Engineering Reference
In-Depth Information
recombinant SOD treatment can prevent the neutrophil influx to the air-
spaces and IL-8 release induced by cigarette smoking through a mechanism
involving downregulation of NF-
k
B (109). This holds great promise if
compounds can be developed with antioxidant enzyme properties which
may be able to act as novel anti-inflammatory drugs by regulating the
molecular events in lung inflammation.
C. Other Auxiliary Antioxidants
Another approach would simply be to supplement diet with small molecular
weight antioxidants. This has been attempted in cigarette smokers using var-
ious antioxidants such as vitamin C and vitamin E (110). The results have
been rather disappointing, although as described in Sec. IX, the antioxidant
vitamin E has been shown to reduce oxidative stress in patients with COPD
(111). Dietrich et al. (112) have recently shown that vitamin C or an antiox-
idant mixture containing vitamin C,
a
-lipoic acid, and vitamin E decreases
plasma F
2
-isoprostane levels in smokers with high body mass index
suggesting that smoking-mediated oxidative stress is involved in lipid
peroxidation. This suggests a variety of multiple antioxidants to protect
against cigarette smoke mediated oxidative stress.
D. Thiol Compounds
1.
N
-acetyl-
l
-cysteine (NAC)
NAC, a cysteine-donating reducing compound, acts as a cellular precursor
of GSH and becomes de-acetylated in the gut to cysteine following oral
administration. NAC may also reduce cystine to cysteine, which is an
important mechanism for intracellular GSH elevation in vivo in lungs. It
reduces disulfide bonds (a property of a good reducing agent), but also
has the potential to interact directly with oxidants. NAC is also used as a
mucolytic agent (to reduce mucus viscosity and to improve mucociliary
clearance).
Pharmacological approaches, particularly with thiol antioxidants,
such as NAC have been used in an attempt to enhance lung GSH in patients
with COPD with varying success (113,114). There have also been studies of
patients with COPD where the administration of NAC has lead to a conflict-
ing result, the number of exacerbations of COPD having been modified
(114,115). This probably arose as a result of differing dosage regimens
and disease severity in these studies (116). A multicenter study using NAC
by metered dose inhalers in patients with chronic cough failed to show a
positive effect on well being, sensation of dyspnoea, cough, or lung function
(116). Van Schooten et al. (117) have reported that supplementation of
oral dose of 600mg twice daily for a period of 6 months in a randomized,
double-blind, placebo-controlled, Phase II chemoprevention trial redu-
ced various plasma and BAL fluid oxidative biomarkers in smokers.
