Nitrative stress, oxidative stress and plasma endothelin levels after inhalation of particulate matter and ozone
- DOI
- Language of the publication
- English
- Date
- 2015-09-17
- Type
- Article
- Author(s)
- Kumarathasan, Prem
- Blais, Erica
- Saravanamuthu, Anushuyadevi
- Bielecki, Agnieszka
- Mukherjee, Ballari
- Bjarnason, Stephen
- Guénette, Josée
- Goegan, Patrick
- Vincent, Renaud
- Publisher
- BMC
Abstract
Background: While exposure to ambient air contaminants is clearly associated with adverse health outcomes, disentangling mechanisms of pollutant interactions remains a challenge. Objectives: 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.
Plain language summary
Health Canada is responsible for assessing the health impacts of air pollution as part of the Clean Air Regulatory Agenda. While exposure to increased levels of air pollution is known to affect heart and lung health, there is little current understanding of how exposure to air pollution causes these adverse health outcomes and what types of effects are caused by exposure to single pollutants vs. mixtures of air pollutants. In this study, Health Canada scientists aimed to characterize changes in markers of free radical reactions and cardiovascular health in rats after inhalation of urban particulate matter, ozone, or a combination of particles plus ozone. The results indicated that there were pollutant-specific changes in oxidative stress and nitrative stress pathways induced by these exposures. The induction of oxidative and nitrative stress, in turn, can cause changes in the levels of circulatory molecules known as endothelins, which are proteins that constrict blood vessels to raise blood pressure. These changes could modulate a number of disease processes, if compensatory mechanisms are not viable. Health Canada will use the results of this study to fill gaps in knowledge in the assessment of health risks related to air pollutant exposures.
Subject
- Health,
- Health and safety