Biomedical Engineering Reference
In-Depth Information
Figure 15
Schematic diagram showing oxidant- and TNF-
a
-mediated activation of
NF-
k
B and IL-8 release. Both NF-
k
B and IL-8 release are inhibited by thiol antiox-
idants, such as NAC and NAL.
been tried through intravenous administration of GSH, oral ingestion of
GSH, and aerosol
=
inhalation of nebulized GSH in an attempt to reduce
inflammation in various lung diseases (2,44). However, all these lead to
undesirable effects suggesting that GSH aerosol therapy may not be an
appropriate way of increasing GSH levels in lung ELF and cells in COPD.
In all of these studies, the question was raised about the bioavailability of
GSH, pH, and osmalility at the site of microenvironment and the resultant
formation of toxic products (GSSG and GSH-adducts). It seems rational to
suggest that neutralizing the pH, providing GSH in salt form, liposome-
entrapped GSH delivery and the maintenance of isotonicity would be useful
in designing any GSH inhalation therapy in inflammatory lung diseases.
Increasing the activity of
g
-GCS by gene transfer techniques may increase
cellular GSH levels. The induction of
g
-GCS by molecular means to increase
cellular GSH levels or
g
GCS gene therapy also holds great promise
in protection against chronic inflammation and oxidant-mediated injury in
COPD.
E. Glutathione Peroxidase Mimic
This is based on the approach that glutathione peroxidase be manipulated
by small molecules with activity similar to this enzyme. Ebselen is seleno-
organic compound, as it contains selenium, an important element in the glu-
tathione peroxidase catalysis of the reaction between GSH and ROS. This
increases the efficiency of GSH as an antioxidant, and can thus be used as
a therapy against oxidative stress and inflammation. Recent studies have
shown that ebselen inhibits airway inflammation (neutrophil recruitment
and chemokine expression) in response to lipopolysaccharide in various
