气候变化领域集成服务门户

Context: Ozone (O-3) exposure is associated with a disruption of iron homeostasis and increased availability of this metal which potentially contributes to an oxidative stress and biological effects.

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 O-3 exposure.

Results: Exposure to 0.4 ppm O-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 mu M ferric ammonium citrate (FAC) for 4 h diminished changes in both SOD1 and COX2 following O-3 exposure. mRNA transcript levels and associated protein release of the pro-inflammatory mediators IL-6 and IL-8 were increased by O-3 exposure of NHBE cells; changes in these endpoints after O-3 exposure were significantly decreased by FAC pre-treatment of the cells. Exposure of CD-1 mice to 2 ppm O-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 0.3ppm O-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 O-3 exposure does not augment biological effects. On the contrary, increased available iron decreases the biological effects of O-3 exposure in cells, animals and humans.