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Antioxidant-mediated augmentation of ozone-induced membrane oxidation
Carol A Ballinger1, Rafael Cueto, Giuseppe Squadrito
1Department of Environmental Health Sciences, School of Public Health, RBPH 530, 1530 3rd Avenue South, University of Alabama at Birmingham, Birmingham, AL 35294-0022, USA.
Free Radical Biology & Medicine
|January 15, 2005
Summary
Inhaled ozone (O3) causes lung cell damage through reactions with antioxidants like ascorbic acid (AH2) and glutathione (GSH) in the epithelial lining fluid (ELF). These reactions generate secondary oxidants that damage cell membranes.
Area of Science:
- Pulmonary toxicology
- Oxidative stress mechanisms
- Airway epithelial cell injury
Background:
- Pulmonary epithelial lining fluid (ELF) contains antioxidants (ascorbic acid, uric acid, glutathione) and lipids susceptible to reaction with inhaled ozone (O3).
- Ozone absorption into the lung may be driven by reactions at the gas/liquid interface, potentially limiting its diffusion to underlying cells.
- Understanding O3-ELF interactions is crucial for elucidating mechanisms of ozone-induced lung injury.
Purpose of the Study:
- To investigate how ozone (O3) interacts with components of the lung's epithelial lining fluid (ELF).
- To determine the role of ELF antioxidants in mediating O3-induced damage to cell membranes.
- To identify potential secondary reactive species responsible for O3-induced cellular damage.
Main Methods:
- A red cell membrane (RCM) model with an aqueous film was used to simulate lung surface compartmentation.
- Evaluated O3 exposure effects on acetylcholinesterase activity (AChE) and TBARS accumulation in the RCM model.
- Assessed O3 reactions with various ELF components (ascorbic acid, uric acid, glutathione, albumin) and bronchoalveolar lavage fluid (BALF).
Main Results:
- Ozone alone did not damage RCMs; however, reactions with ascorbic acid (AH2) and glutathione (GSH) caused dose-dependent oxidative damage.
- AH2-mediated oxidation was independent of superoxide dismutase, catalase, mannitol, or iron chelators, suggesting non-radical pathways.
- Ozone reactions with uric acid or albumin alone did not cause damage, but combined with AH2, RCM oxidation occurred. Rat BALF induced RCM oxidation, which was reduced by in vivo O3 exposure.
Conclusions:
- Secondary products from O3 reactions with ELF antioxidants (AH2, GSH) are likely initiators of red cell membrane oxidation.
- These ozone-derived reactive species, potentially including singlet oxygen (1O2), may explain ozone's ability to permeate the ELF and cause cellular damage.
- The findings highlight the critical role of ELF antioxidants in modulating ozone's toxicity and suggest secondary reactive species are key mediators of lung injury.