title: Nitrative stress, oxidative stress and plasma endothelin levels after inhalation of particulate matter and ozone.
abstract: BACKGROUND
  While exposure to ambient air contaminants is clearly associated with adverse health outcomes, disentangling mechanisms of pollutant interactions remains a challenge.
  
  
  OBJECTIVE
  We aimed at characterizing free radical pathways and the endothelinergic system in rats after inhalation of urban particulate matter, ozone, and a combination of particles plus ozone to gain insight into pollutant-specific toxicity mechanisms and any effect modification due to air pollutant mixtures.
  
  
  METHODS
  Fischer 344 rats were exposed for 4 h to a 3 × 3 concentration matrix of ozone (0, 0.4, 0.8 ppm) and EHC-93 particles (0, 5, 50 mg/m(3)). Bronchoalveolar lavage fluid (BALF), BAL cells, blood and plasma were analysed for biomarkers of effects immediately and 24 h post-exposure.
  
  
  RESULTS
  Inhalation of ozone increased (p < 0.05) lipid oxidation products in BAL cells immediately post-exposure, and increased (p < 0.05) total protein, neutrophils and mature macrophages in the BALF 24 h post-exposure. Ozone increased (p < 0.05) the formation of reactive oxygen species (ROS), assessed by m-, p-, o-tyrosines in BALF (Ozone main effects, p < 0.05), while formation of reactive nitrogen species (RNS), indicated by 3-nitrotyrosine, correlated with dose of urban particles (EHC-93 main effects or EHC-93 × Ozone interactions, p < 0.05). Carboxyhemoglobin levels in blood exhibited particle exposure-related increase (p < 0.05) 24 h post recovery. Plasma 3-nitrotyrosine and o-tyrosine were increased (p < 0.05) after inhalation of particles; the effect on 3-nitrotyrosine was abrogated after exposure to ozone plus particles (EHC-93 × Ozone, p < 0.05). Big endothelin-1 (BET-1) and ET-1 were increased in plasma after inhalation of particles or ozone alone, but the effects appeared to be attenuated by co-exposure to contaminants (EHC-93 × Ozone, p < 0.05). Plasma ET levels were positively correlated (p < 0.05) with BALF m- and o-tyrosine levels.
  
  
  CONCLUSIONS
  Pollutant-specific changes can be amplified or abrogated following multi-pollutant exposures. Oxidative and nitrative stress in the lung compartment may contribute to secondary extra-pulmonary ROS/RNS formation. Nitrative stress and endothelinergic imbalance emerge as potential key pathways of air pollutant health effects, notably of ambient particulate matter.
authors.affiliation: Analytical Biochemistry and Proteomics Laboratory, Environmental Health Centre, Room 233A, 0803C Tunney's Pasture, Ottawa, K1A 0 K9, ON, Canada. premkumari.kumarathasan@hc-sc.gc.ca.
authors.forename: Prem
authors.initials: P
authors.lastname: Kumarathasan
authors.affiliation: Analytical Biochemistry and Proteomics Laboratory, Environmental Health Centre, Room 233A, 0803C Tunney's Pasture, Ottawa, K1A 0 K9, ON, Canada.
authors.forename: Erica
authors.initials: E
authors.lastname: Blais
authors.affiliation: Analytical Biochemistry and Proteomics Laboratory, Environmental Health Centre, Room 233A, 0803C Tunney's Pasture, Ottawa, K1A 0 K9, ON, Canada.
authors.forename: Anushuyadevi
authors.initials: A
authors.lastname: Saravanamuthu
authors.affiliation: Analytical Biochemistry and Proteomics Laboratory, Environmental Health Centre, Room 233A, 0803C Tunney's Pasture, Ottawa, K1A 0 K9, ON, Canada.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bielecki
authors.affiliation: Analytical Biochemistry and Proteomics Laboratory, Environmental Health Centre, Room 233A, 0803C Tunney's Pasture, Ottawa, K1A 0 K9, ON, Canada.
authors.forename: Ballari
authors.initials: B
authors.lastname: Mukherjee
authors.affiliation: Inhalation Toxicology Laboratory, Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, K1A 0 K9, ON, Canada.
authors.forename: Stephen
authors.initials: S
authors.lastname: Bjarnason
authors.affiliation: Inhalation Toxicology Laboratory, Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, K1A 0 K9, ON, Canada.
authors.forename: Josée
authors.initials: J
authors.lastname: Guénette
authors.affiliation: Inhalation Toxicology Laboratory, Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, K1A 0 K9, ON, Canada.
authors.forename: Patrick
authors.initials: P
authors.lastname: Goegan
authors.affiliation: Inhalation Toxicology Laboratory, Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, K1A 0 K9, ON, Canada.
authors.forename: Renaud
authors.initials: R
authors.lastname: Vincent
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D016232:Endothelins / Q000097:blood*; D019570:Inhalation Exposure; D009566:Nitrates / Q000378:metabolism*; D018384:Oxidative Stress; D010126:Ozone / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D015415:Biomarkers; D016232:Endothelins; D009566:Nitrates; D010126:Ozone