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.

BackgroundThere is a paucity of mechanistic information that is central to the understanding of the adverse health effects of source emission exposures. To identify source emission-related effects, blood and saliva samples from healthy volunteers who spent five days near a steel plant (Bayview site, with and without a mask that filtered many criteria pollutants) and at a well-removed College site were tested for oxidative stress, inflammation and endothelial dysfunction markers.MethodsBiomarker analyses were done using multiplexed protein-array, HPLC-Fluorescence, EIA and ELISA methods. Mixed effects models were used to test for associations between exposure, biological markers and physiological outcomes. Heat map with hierarchical clustering and Ingenuity Pathway Analysis (IPA) were used for mechanistic analyses.ResultsMean CO, SO2 and ultrafine particles (UFP) levels on the day of biological sampling were higher at the Bayview site compared to College site. Bayview site exposures “without” mask were associated with increased (p < 0.05) pro-inflammatory cytokines (e.g IL-4, IL-6) and endothelins (ETs) compared to College site. Plasma IL-1β, IL-2 were increased (p < 0.05) after Bayview site “without” compared to “with” mask exposures. Interquartile range (IQR) increases in CO, UFP and SO2 were associated with increased (p < 0.05) plasma pro-inflammatory cytokines (e.g. IL-6, IL-8) and ET-1(1–21) levels. Plasma/saliva BET-1 levels were positively associated (p < 0.05) with increased systolic BP. C-reactive protein (CRP) was positively associated (p < 0.05) with increased heart rate. Protein network analyses exhibited activation of distinct inflammatory mechanisms after “with” and “without” mask exposures at the Bayview site relative to College site exposures.ConclusionsThese findings suggest that air pollutants in the proximity of steel mill site can influence inflammatory and vascular mechanisms. Use of mask and multiple biomarker data can be valuable in gaining insight into source emission-related health impacts.Electronic supplementary materialThe online version of this article (10.1186/s12989-018-0270-4) contains supplementary material, which is available to authorized users.

HLE cell-line exhibited a bi-phasic response in terms of cell viability, ROS and RNS profiles. At doses <0.5 Gy, ROS and RNS levels were lower than control and at higher doses (>0.5 Gy) a steady increase was observed in each metabolite. This response was observed irrespective of dose-rate. Among the associations tested, cl, p, m-tyrosine and 3-nitrotyrosine revealed changes (p < .05) at 5 Gy compared exclusively to 0.05 and 0.01 Gy. In addition, dose-rate related differences were observed. Overall, the data suggests that ROS and RNS are key events in radiation induced damage and this response is dependent on the dose and dose-rate of IR exposure.

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ObjectiveNeonatal morbidity and mortality can be influenced by maternal health status. Information on maternal and fetal biomarkers of adverse health outcomes is limited. This work aims at identifying maternal biomarkers associated with low and high birth weight for gestational age groups.Design and settingsPopulation-based prospective cohort study of the potential adverse health effects of exposure to environmental contaminants on pregnancy and infant health.MethodsThird trimester maternal plasma samples (n = 1588) from a pregnancy cohort (Maternal-Infant Research on Environmental Chemicals Study, MIREC) were analyzed for changes in a target spectrum of biomarkers of vascular health (e.g., matrix metalloproteinases MMPs, vascular endothelial cell growth factor VEGF), inflammation (e.g. cellular adhesion molecules CAMs, cytokines, chemokines) by affinity-based multiplex protein array analyses. Multivariate logistic regression analyses were done to examine associations between target plasma biomarkers, maternal-infant characteristics, and birth weight outcomes assessed as small for gestational age (SGA) ≤10th percentile and large for gestational age (LGA) ≥90th percentile groups.Results and outcomesOur results revealed that maternal plasma biomarkers monocyte chemoattractant protein-1 MCP-1 (p<0.05, +ve) and VEGF (p<0.05, -ve) along with parity = 1 (p<0.01, -ve) and gestational hypertension (p<0.05, +ve) were associated with SGA births. Meanwhile, LGA was associated with maternal plasma VEGF (p<0.05, +ve) and MMP-9 (p<0.05, -ve) and gestational hypertension (p<0.01, +ve), pre-pregnancy body mass index (p<0.01, +ve), parity (p<0.05, +ve) and education (p<0.05, -ve).ConclusionsThird trimester maternal plasma biomarkers in combination with maternal health and socioeconomic characteristics can be useful in predicting SGA and LGA outcomes. Maternal vascular health and inflammatory status may contribute to both SGA and LGA births through distinct molecular mechanisms.