title: Antioxidant components of naturally-occurring oils exhibit marked anti-inflammatory activity in epithelial cells of the human upper respiratory system.
abstract: BACKGROUND
  The upper respiratory tract functions to protect lower respiratory structures from chemical and biological agents in inspired air. Cellular oxidative stress leading to acute and chronic inflammation contributes to the resultant pathology in many of these exposures and is typical of allergic disease, chronic sinusitis, pollutant exposure, and bacterial and viral infections. Little is known about the effective means by which topical treatment of the nose can strengthen its antioxidant and anti-inflammatory defenses. The present study was undertaken to determine if naturally-occurring plant oils with reported antioxidant activity can provide mechanisms through which upper respiratory protection might occur.
  
  
  METHODS
  Controlled exposure of the upper respiratory system to ozone and nasal biopsy were carried out in healthy human subjects to assess mitigation of the ozone-induced inflammatory response and to assess gene expression in the nasal mucosa induced by a mixture of five naturally-occurring antioxidant oils--aloe, coconut, orange, peppermint and vitamin E. Cells of the BEAS-2B and NCI-H23 epithelial cell lines were used to investigate the source and potential intracellular mechanisms of action responsible for oil-induced anti-inflammatory activity.
  
  
  RESULTS
  Aerosolized pretreatment with the mixed oil preparation significantly attenuated ozone-induced nasal inflammation. Although most oil components may reduce oxidant stress by undergoing reduction, orange oil was demonstrated to have the ability to induce long-lasting gene expression of several antioxidant enzymes linked to Nrf2, including HO-1, NQO1, GCLm and GCLc, and to mitigate the pro-inflammatory signaling of endotoxin in cell culture systems. Nrf2 activation was demonstrated. Treatment with the aerosolized oil preparation increased baseline levels of nasal mucosal HO-1 expression in 9 of 12 subjects.
  
  
  CONCLUSIONS
  These data indicate that selected oil-based antioxidant preparations can effectively reduce inflammation associated with oxidant stress-related challenge to the nasal mucosa. The potential for some oils to activate intracellular antioxidant pathways may provide a powerful mechanism through which effective and persistent cytoprotection against airborne environmental exposures can be provided in the upper respiratory mucosa.
authors.affiliation: Health Effects Assessment Laboratory, Department of Environmental Health Sciences, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.
authors.forename: Meixia
authors.initials: M
authors.lastname: Gao
authors.forename: Anju
authors.initials: A
authors.lastname: Singh
authors.forename: Kristin
authors.initials: K
authors.lastname: Macri
authors.forename: Curt
authors.initials: C
authors.lastname: Reynolds
authors.forename: Vandana
authors.initials: V
authors.lastname: Singhal
authors.forename: Shyam
authors.initials: S
authors.lastname: Biswal
authors.forename: Ernst W
authors.initials: EW
authors.lastname: Spannhake
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D001706:Biopsy; D002460:Cell Line; D018592:Cross-Over Studies; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009297:Nasal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010126:Ozone; D010938:Plant Oils / Q000008:administration & dosage / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D012220:Rhinitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: D000336:Aerosols; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018836:Inflammation Mediators; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010938:Plant Oils; D012333:RNA, Messenger; D010126:Ozone; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1