ABSTRACT
This chapter discusses therapeutic approaches to mitigate or prevent oxidant-
generated pathology in lung injury. Throughout life, lung cells encounter several-fold higher oxygen concentrations than present in utero, and are thus
exposed to relative oxidative stress. Furthermore, a number of lung diseases
in newborns and older individuals necessitate the administration of higher than
atmospheric concentrations of oxygen. Reactive oxygen and nitrogen species
have been implicated in the pathogenesis of various forms of lung injury as
detailed in earlier chapters (e.g., Chapter 7). In the normal lungs, the activity
of reactive oxygen species (ROS) is antagonized by intracellular and extracel-
lular antioxidant substances. The elaborate endogenous antioxidant system includes classical antioxidant enzymes (AOEs), glutathione, and thioredoxin
with their associated redox cycles, heme oxygenases, and numerous small
molecular weight antioxidants. This chapter considers therapeutic agents that
can supplement or substitute for endogenous antioxidants if they are depleted
or overwhelmed during lung injury. An ideal antioxidant therapeutic agent,
either natural or synthetic, should have good bioavailability, and it should be
potent in penetrating to site of action and efficient in scavenging appropriate
radical species. The agent should be stable, nontoxic, nonimmunogenic, and preferably inexpensive. Importantly, it should allow essential developmental
and healing processes to proceed. Awide variety of antioxidant agents, includ-
ing classical AOEs, catalytic antioxidants and antibodies, thiol-based antioxi-
dants, vitamins, lazaroids, and novel antioxidant approaches have been
investigated in experimental models in vitro and in vivo in an attempt to pre-
vent or ameliorate lung injury. Although research indicates favorable responses to several antioxidant compounds, the usefulness of these agents in the treat-
ment of human lung injury and respiratory disease has yet to be fully explored.
