title: Iron decreases biological effects of ozone exposure.
abstract: BACKGROUND
  Ozone (O₃) 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 O₃ exposure.
  
  
  RESULTS
  Exposure to 0.4 ppm O₃ 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 µM ferric ammonium citrate (FAC) for 4 h diminished changes in both SOD1 and COX2 following O₃ exposure. mRNA transcript levels and associated protein release of the pro-inflammatory mediators IL-6 and IL-8 were increased by O₃ exposure of NHBE cells; changes in these endpoints after O₃ exposure were significantly decreased by FAC pre-treatment of the cells. Exposure of CD-1 mice to 2 ppm O₃ 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 O₃ for 2 h demonstrated significant correlations with either their pre-exposure plasma ferritin or iron concentrations.
  
  
  CONCLUSIONS
  We conclude that greater availability of iron after O₃ exposure does not augment biological effects. On the contrary, increased available iron decreases the biological effects of O₃ exposure in cells, animals and humans.
authors.affiliation: National Health and Environmental Effects Research Laboratory, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park , NC , USA and.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ghio
authors.forename: Joleen M
authors.initials: JM
authors.lastname: Soukup
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Dailey
authors.forename: Judy H
authors.initials: JH
authors.lastname: Richards
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Duncan
authors.forename: James
authors.initials: J
authors.lastname: Lehmann
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D021461:Animals, Outbred Strains; D000931:Antidotes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005293:Ferritins / Q000097:blood / Q000378:metabolism; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects; D007501:Iron / Q000032:analysis / Q000097:blood; D008297:Male; D051379:Mice; D009752:Nutritional Status; D010083:Oxidants, Photochemical / Q000737:chemistry / Q000633:toxicity; D010126:Ozone / Q000037:antagonists & inhibitors* / Q000633:toxicity; D011014:Pneumonia / Q000097:blood / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012129:Respiratory Function Tests; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D000931:Antidotes; D005290:Ferric Compounds; D010083:Oxidants, Photochemical; D000644:Quaternary Ammonium Compounds; D010126:Ozone; D005293:Ferritins; D007501:Iron; C013531:ferric ammonium citrate
keywords: Air pollution; ferritin; free radicals; lung diseases; oxidants