Inflammatory
lung diseases are characterized by chronic
inflammation and
oxidant/
antioxidant imbalance. The sources of the increased oxidative stress in patients with chronic inflammatory
lung diseases such as
asthma and
chronic obstructive pulmonary disease (
COPD) derive from the increased burden of inhaled
oxidants, and from the increased amounts of
reactive oxygen species (ROS) generated by several inflammatory, immune and various structural cells of the airways. Increased levels of ROS produced in the airways is reflected by increased markers of oxidative stress in the airspaces, sputum, breath, lungs and blood in patients with
lung diseases. ROS, either directly or via the formation of lipid peroxidation products such as
4-hydroxy-2-nonenal may play a role in enhancing the
inflammation through the activation of stress
kinases (JNK,
MAPK, p38) and redox sensitive
transcription factors such as NF-capital KJE, MacedonianB and
AP-1. Recent evidences have indicated that oxidative stress and pro-inflammatory mediators can alter nuclear
histone acetylation/deacetylation allowing access for
transcription factor DNA binding leading to enhanced pro-inflammatory gene expression in various lung cells. Understanding of the mechanisms of redox signaling,
NF-kappaB/AP-1 regulation, the balance between
histone acetylation and deacetylation and the release and expression of pro- and antiinflammatory mediators may lead to the development of novel
therapies based on the pharmacological manipulation of
antioxidants in
lung inflammation and injury.
Antioxidants that have effective wide spectrum activity and good bioavailability,
thiols or molecules which have dual
antioxidant and anti-inflammatory activity, may be potential therapeutic agents which not only protect against the direct injurious effects of
oxidants, but may fundamentally alter the underlying inflammatory processes which play an important role in the pathogenesis of chronic inflammatory
lung diseases.