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Iron decreases biological effects of ozone exposure
Ghio, Andy, J. Soukup, L. Dailey, J. Richards, K. Duncan, AND J. Lehmann. Iron decreases biological effects of ozone exposure. INHALATION TOXICOLOGY. Taylor & Francis, Inc., Philadelphia, PA, 26(7):391-399, (2014).
Ozone (O3) is a major component of air pollution and many locales in the United States exceed the National Ambient Air Quality Standard for ground level ozone recommended by the Environmental Protection Agency presenting a health risk.
CONTEXT: Ozone (0(3)) exposure is associated with a disruption of iron homeostasis and increased availability of this metal which potentially contributes to an oxidative stress and biologicaleffects. OBJECTIVE: We tested the postulate that increased concentrations of iron in cells, an animal model and human subjects would significantly impact the biological effects of 0(3) exposure. RESULTS: Exposure to 0.4 ppm 0(3) for 5 h increased mRNA for both Superoxide Dismutase-1 (SOD1) and Cyclooxygenase-2 (COX2) in normal human bronchial epithelial (NHBE) cells. Pre treatment of NHBE cells with 200 uM ferric ammonium citrate (FAC) for 4 h diminished changes in both SOD1 and COX2 following 0(3) exposure. mRNA transcript levels and associated protein release of the pro-inflammatory mediators IL-6 and IL-8 were increased by 0(3) exposure of NHBE cells; changes in these endpoints after 0(3) exposure were significantly decreased by FAC pre-treatment of the cells. Exposure of CD-1 mice to 2 ppm 0(3) for 3 h significantly increased lavage indices of inflammation and airflow limitation. Pre-treatment of the animals with pharyngeal aspiration of FAC diminished the same endpoints. Finally, the mean loss of pulmonary function in 19 healthy volunteers exposed to 0.3 ppm 0(3) for 2 h demonstrated significant correlations with either their pre-exposure plasma ferritin or iron concentrations. DISCUSSION AND CONCLUSION: We conclude that greater availability of iron after 0(3) exposure does not augment biological effects. On the contrary, increased available iron decreases the biological effects of 0(3) exposure in cells, animals and humans