Abstract
BackgroundWhile exposure to ambient air contaminants is clearly associated with adverse health outcomes, disentangling mechanisms of pollutant interactions remains a challenge.ObjectivesWe 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.MethodsFischer 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/m3). Bronchoalveolar lavage fluid (BALF), BAL cells, blood and plasma were analysed for biomarkers of effects immediately and 24 h post-exposure.ResultsInhalation 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.ConclusionsPollutant-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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-015-0103-7) contains supplementary material, which is available to authorized users.
Highlights
While exposure to ambient air contaminants is clearly associated with adverse health outcomes, disentangling mechanisms of pollutant interactions remains a challenge
Oxidative and nitrative stress in the lung compartment may contribute to secondary extra-pulmonary reactive oxygen species (ROS)/reactive nitrogen species (RNS) formation
Lung injury markers Total BAL cells were decreased by 20 % immediately postexposure to 0.8 ppm O3 but increased slightly 24 h postexposure (Fig. 1a; 3-way ANOVA, Ozone x Recovery, p < 0.001), a pattern of change attributed to the total macrophage population (Fig. 1b; 3-way ANOVA, Ozone × Recovery, p = 0.001; 2-way ANOVA, Ozone × EHC-93, p = 0.024)
Summary
While exposure to ambient air contaminants is clearly associated with adverse health outcomes, disentangling mechanisms of pollutant interactions remains a challenge. Episodic increases in ambient air contaminant levels have clearly been associated with increased respiratory and cardiovascular morbidity and mortality [1,2,3]. Air pollution has been implicated in diverse health impacts such as stroke, Alzheimer’s pathology, mood disorders, gastrointestinal disorders, low infant birth weight and cancer [5,6,7,8,9,10]. Notwithstanding the strong evidence for adverse health impacts of ambient air pollutants, there remain important knowledge gaps in our understanding of the toxicity mechanisms and the biological plausibility of adverse health outcomes [11]. Understanding of the toxicodynamics of ambient air pollutants and their interactions should allow the development of risk estimate models grounded on direct evidence
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