Project: Research project

Project Details


The toxic gases O3, NO2 and cigarette smoke (CS) cause lung damage. The
cellular and molecular mechanisms of the damage are complex, but oxidant
reactions are thought to play a major role. The respiratory tract
epithelial lining fluids (RTLFs) are among the first biological systems to
come into contact with inhaled gases. RTLFs contain many different
antioxidants, including mucin, uric acid, alpha-tocopherol, ascorbic acid,
and glutathione. Although much is known about the reactions of individual
isolated antioxidants with oxidants, very little is known about the
integrated antioxidant defenses of RTLFs from different parts of the
respiratory tract. RTLFs may not only protect against oxidative injury to
underlying cells, but oxidation of their constituents may generate
cytotoxic products. In addition, several of their protein and lipid
constituents have specific functions, such as elastase-inhibiting capacity
and surface tension-lowering ability. The applicants will apply a strategy
in which temporal losses of different antioxidants are quantitated in
relation to the onset of structural and functional protein and lipid damage
in RTLFs exposed to O3, NO2 and CS. The cellular effects of oxidized RTLFs
will also be examined. The specific aims are: (i) to identify the
antioxidants present in RTLFs from different parts of the respiratory
tract; (ii) to identify the most important antioxidants in RTLFs that can
protect the proteins and lipids present against damage by O3, NO2 and CS,
singly or in combination; (iii) to study the effects of oxidation of RTLF
components upon their cytoxicity and their biochemical functions. Highly-
sensitive, specific assays will be used to measure antioxidants, lipid
peroxidation and oxidative damage to proteins. Understanding the
integrated protective role of antioxidants in RTLFs may well provide new
insights into the sequence of biochemical and cellular events occurring in
the respiratory tract after exposure to toxic gases. This may lead to the
development of strategies for protective therapeutic interventions and of
"biomarkers" for O3-induced damage.
Effective start/end date7/15/925/31/02


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $167,015.00
  • National Institutes of Health


  • Medicine(all)


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