Peat smoke inhalation alters blood pressure, baroreflex sensitivity, and cardiac arrhythmia risk in rats.

Wildland fires (WF) are linked to adverse health impacts related to poor air quality. The cardiovascular impacts of emissions from specific biomass sources are however unknown. The purpose of this study was to assess the cardiovascular impacts of a single exposure to peat smoke, a key regional WF air pollution source, and relate these to baroreceptor sensitivity and inflammation. Three-month-old male Wistar-Kyoto rats, implanted with radiotelemeters for continuous monitoring of heart rate (HR), blood pressure (BP), and spontaneous baroreflex sensitivity (BRS), were exposed once, for 1-hr, to filtered air or low (0.38 mg/m3 PM) or high (4.04 mg/m3) concentrations of peat smoke. Systemic markers of inflammation and sensitivity to aconitine-induced cardiac arrhythmias, a measure of latent myocardial vulnerability, were assessed in separate cohorts of rats 24 hr after exposure. PM size (low peat = 0.4-0.5 microns vs. high peat = 0.8-1.2 microns) and proportion of organic carbon (low peat = 77% vs. high peat = 65%) varied with exposure level. Exposure to high peat and to a lesser extent low peat increased systolic and diastolic BP relative to filtered air. In contrast, only exposure to low peat elevated BRS and aconitine-induced arrhythmogenesis relative to filtered air and increased circulating levels of low-density lipoprotein cholesterol, complement components C3 and C4, angiotensin-converting enzyme (ACE), and white blood cells. Taken together, exposure to peat smoke produced overt and latent cardiovascular consequences that were likely influenced by physicochemical characteristics of the smoke and associated adaptive homeostatic mechanisms.

A single exposure to eucalyptus smoke sensitizes rats to the postprandial cardiovascular effects of a high carbohydrate oral load.

OBJECTIVE: Previous studies have shown that air pollution exposure primes the body to heightened responses to everyday stressors of the cardiovascular system. The purpose of this study was to examine the utility of postprandial responses to a high carbohydrate oral load, a cardiometabolic stressor long used to predict cardiovascular risk, in assessing the impacts of exposure to eucalyptus smoke (ES), a contributor to wildland fire air pollution in the Western coast of the United States. MATERIALS AND METHODS: Three-month-old male Sprague Dawley rats were exposed once (1 h) to filtered air (FA) or ES (700 µg/m3 fine particulate matter), generated by burning eucalyptus in a tube furnace. Rats were then fasted for six hours the following morning, and subsequently administered an oral gavage of either water or a HC suspension (70 kcal% from carbohydrate), mimicking a HC meal. Two hours post gavage, cardiovascular ultrasound, cardiac pressure-volume (PV), and baroreceptor sensitivity assessments were made, and pulmonary and systemic markers assessed. RESULTS: ES inhalation alone increased serum interleukin (IL)-4 and nasal airway levels of gamma glutamyl transferase. HC gavage alone increased blood glucose, blood pressure, and serum IL-6 and IL-13 compared to water vehicle. By contrast, only ES-exposed and HC-challenged animals had increased PV loop measures of cardiac output, ejection fraction %, dP/dtmax, dP/dtmin, and stroke work compared to ES exposure alone and/or HC challenge alone. DISCUSSION AND CONCLUSIONS: Exposure to a model wildfire air pollution source modifies cardiovascular responses to HC challenge, suggesting air pollution sensitizes the body to systemic triggers.

The role of fuel type and combustion phase on the toxicity of biomass smoke following inhalation exposure in mice.

The characteristics of wildland fire smoke exposures which initiate or exacerbate cardiopulmonary conditions are unclear. We previously reported that, on a mass basis, lung toxicity associated with particulate matter (PM) from flaming smoke aspirated into mouse lungs is greater than smoldering PM. In this study, we developed a computer-controlled inhalation system which can precisely control complex biomass smoke emissions from different combustion conditions. This system was used to examine the toxicity of inhaled biomass smoke from peat, eucalyptus, and oak fuels generated under smoldering and flaming phases with emissions set to the same approximate concentration of carbon monoxide (CO) for each exposure (60-110 ppm), resulting in PM levels of ~ 4 mg/m3 for flaming and ~ 40 mg/m3 for smoldering conditions. Mice were exposed by inhalation 1 h/day for 2 days, and assessed for lung toxicity at 4 and 24 h after the final exposure. Peat (flaming and smoldering) and eucalyptus (smoldering) smoke elicited significant inflammation (neutrophil influx) in mouse lungs at 4 h with the peat (flaming) smoke causing even greater lung inflammation at 24-h post-exposure. A significant alteration in ventilatory timing was also observed in mice exposed to the peat (flaming) and eucalyptus (flaming and smoldering) smoke immediately after each day of exposure. No responses were seen for exposures to similar concentrations of flaming or smoldering oak smoke. The lung toxicity potencies (neutrophil influx per PM mass) agreed well between the inhalation and previously reported aspiration studies, demonstrating that although flaming smoke contains much less PM mass than smoldering smoke, it is more toxic on a mass basis than smoldering smoke exposure, and that fuel type is also a controlling factor.

Smoldering and flaming biomass wood smoke inhibit respiratory responses in mice.

Background: Acute and chronic exposures to biomass wildfire smoke pose significant health risks to firefighters and impacted communities. Susceptible populations such as asthmatics may be particularly sensitive to wildfire effects. We examined pulmonary responses to biomass smoke generated from combustion of peat, oak, or eucalyptus in control and house dust mite (HDM)-allergic mice. Methods: Mice were exposed 1 h/d for 2 consecutive days to emissions from each fuel type under smoldering or flaming conditions (∼40 or ∼3.3 mg PM/m3, respectively) while maintaining comparable CO levels (∼60-120 ppm). Results: Control and allergic mice reduced breathing frequency during exposure to all biomass emissions compared with pre-exposure to clean air. Smoldering eucalyptus and oak, but not peat, further reduced frequency compared to flaming conditions in control and allergic groups, while also reducing minute volume and peak inspiratory flow in control mice. Several biochemical and cellular markers of lung injury and inflammation were suppressed by all biomass emission types in both HDM-allergic and control mice. Control mice exposed to flaming eucalyptus at different PM concentrations (C) and times (T) with the same C × T product had a greater decrease in breathing frequency with high concentration acute exposure compared with lower concentration episodic exposure. This decrease was ameliorated by PM HEPA filtration, indicating that the respiratory changes were partially mediated by biomass smoke particles. Conclusion: These data show that exposure to smoldering eucalyptus or oak smoke inhibits respiratory responses to a greater degree than peat smoke. Anti-inflammatory effects of CO may possibly contribute to smoke-induced suppression of allergic inflammatory responses.

Comparative Cardiopulmonary Effects of Particulate Matter- And Ozone-Enhanced Smog Atmospheres in Mice.

This study was conducted to compare the cardiac effects of particulate matter (PM)- (SA-PM) and ozone(O3)-enhanced (SA-O3) smog atmospheres in mice. Based on our previous findings of filtered diesel exhaust we hypothesized that SA-O3 would cause greater cardiac dysfunction than SA-PM. Radiotelemetered mice were exposed to either SA-PM, SA-O3, or filtered air (FA) for 4 h. Heart rate (HR) and electrocardiogram were recorded continuously before, during and after exposure. Both SA-PM and SA-O3 increased heart rate variability (HRV) but only SA-PM increased HR. Normalization of responses to total hydrocarbons, gas-only hydrocarbons and PM concentration were performed to assess the relative contribution of each phase given the compositional variability. Normalization to PM concentration revealed that SA-O3 was more potent in increasing HRV, arrhythmogenesis, and causing ventilatory changes. However, there were no differences when the responses were normalized to total or gas-phase only hydrocarbons. Thus, this study demonstrates that a single exposure to smog causes cardiac effects in mice. Although the responses of SA-PM and SA-O3 are similar, the latter is more potent in causing electrical disturbances and breathing changes potentially due to the effects of irritant gases, which should therefore be accounted for more rigorously in health assessments.

Early-Life Persistent Vitamin D Deficiency Alters Cardiopulmonary Responses to Particulate Matter-Enhanced Atmospheric Smog in Adult Mice.

Early life nutritional deficiencies can lead to increased cardiovascular susceptibility to environmental exposures. Thus, the purpose of this study was to examine the effect of early life persistent vitamin D deficiency (VDD) on the cardiopulmonary response to a particulate matter-enhanced photochemical smog. Mice were fed a VDD or normal diet (ND) after weaning. At 17 weeks of age, mice were implanted with radiotelemeters to monitor electrocardiogram, heart rate (HR), and heart rate variability (HRV). Ventilatory function was measured throughout the diet before and after smog exposure using whole-body plethysmography. VDD mice had lower HR, increased HRV, and decreased tidal volume compared with ND. Regardless of diet, HR decreased during air exposure; this response was blunted by smog in ND mice and to a lesser degree in VDD. When compared with ND, VDD increased HRV during air exposure and more so with smog. However, smog only increased cardiac arrhythmias in ND mice. This study demonstrates that VDD alters the cardiopulmonary response to smog, highlighting the possible influence of nutritional factors in determining responses to air pollution. The mechanism of how VDD induces these effects is currently unknown, but modifiable factors should be considered when performing risk assessment of complex air pollution atmospheres.

Douglas-Fir ( Pseudotsuga menziesii (Mirb.) Franco) Transcriptome Profile Changes Induced by Diesel Emissions Generated with CeO2 Nanoparticle Fuel Borne Catalyst.

It is important to understand molecular effects on plants exposed to compounds released from use of products containing engineered nanomaterials. Here, we present mRNA sequencing data on transcriptome impacts to Douglas-fir following 2 weeks of sublethal exposure to 30:1 diluted airborne emissions released from combustion of diesel fuel containing engineered CeO2 nanoparticle catalysts (DECe). Our hypothesis was that chamber exposure to DECe would induce distinct transcriptome changes in seedling needles compared with responses to conventional diesel exhaust (DE) or filtered DECe Gas Phase. Significantly increased uptake/binding of Ce in needles of DECe treated seedlings was 2.7X above background levels and was associated with altered gene expression patterns. All 225 Blast2GO gene ontologies (GOs) enriched by up-regulated DECe transcripts were nested within GOs for DE, however, 29 of 31 enriched GOs for down-regulated DECe transcripts were unique. MapMan analysis also identified three pathways enriched with DECe down-regulated transcripts. There was prominent representation of genes with attenuated expression in transferase, transporter, RNA regulation and protein degradation GOs and pathways. CeO2 nanoparticle additive decreased and shifted molecular impact of diesel emissions. Wide-spread use of such products and chronic environmental exposure to DECe may adversely affect plant physiology and development.

Photochemical Conversion of Surrogate Emissions for Use in Toxicological Studies: Role of Particulate- and Gas-Phase Products.

The production of photochemical atmospheres under controlled conditions in an irradiation chamber permits the manipulation of parameters that influence the resulting air-pollutant chemistry and potential biological effects. To date, no studies have examined how contrasting atmospheres with a similar Air Quality Health Index (AQHI), but with differing ratios of criteria air pollutants, might differentially affect health end points. Here, we produced two atmospheres with similar AQHIs based on the final concentrations of ozone, nitrogen dioxide, and particulate matter (PM2.5). One simulated atmosphere (SA-PM) generated from irradiation of ∼23 ppmC gasoline, 5 ppmC α-pinene, 529 ppb NO, and 3 µg m-3 (NH4)2SO4 as a seed resulted in an average of 976 µg m-3 PM2.5, 326 ppb NO2, and 141 ppb O3 (AQHI 97.7). The other atmosphere (SA-O3) generated from 8 ppmC gasoline, 5 ppmC isoprene, 874 ppb NO, and 2 µg m-3 (NH4)2SO4 resulted in an average of 55 µg m-3 PM2.5, 643 ppb NO2, and 430 ppb O3 (AQHI of 99.8). Chemical speciation by gas chromatography showed that photo-oxidation degraded the organic precursors and promoted the de novo formation of secondary reaction products such as formaldehyde and acrolein. Further work in accompanying papers describe toxicological outcomes from the two distinct photochemical atmospheres.

Effects of Simulated Smog Atmospheres in Rodent Models of Metabolic and Immunologic Dysfunction.

Air pollution is a diverse and dynamic mixture of gaseous and particulate matter, limiting our understanding of associated adverse health outcomes. The biological effects of two simulated smog atmospheres (SA) with different compositions but similar air quality health indexes were compared in a nonobese diabetic rat model (Goto-Kakizaki, GK) and three mouse immune models (house dust mite (HDM) allergy, antibody response to heat-killed pneumococcus, and resistance to influenza A infection). In GK rats, both SA-PM (high particulate matter) and SA-O3 (high ozone) decreased cholesterol levels immediately after a 4-h exposure, whereas only SA-O3 increased airflow limitation. Airway responsiveness to methacholine was increased in HDM-allergic mice compared with nonallergic mice, but exposure to SA-PM or SA-O3 did not significantly alter responsiveness. Exposure to SA-PM did not affect the IgM response to pneumococcus, and SA-O3 did not affect virus titers, although inflammatory cytokine levels were decreased in mice infected at the end of a 7-day exposure. Collectively, acute SA exposures produced limited health effects in animal models of metabolic and immune diseases. Effects of SA-O3 tended to be greater than those of SA-PM, suggesting that gas-phase components in photochemically derived multipollutant mixtures may be of greater concern than secondary organic aerosol PM.

Evaluation of an Air Quality Health Index for Predicting the Mutagenicity of Simulated Atmospheres.

No study has evaluated the mutagenicity of atmospheres with a calculated air quality health index (AQHI). Thus, we generated in a UV-light-containing reaction chamber two simulated atmospheres (SAs) with similar AQHIs but different proportions of criteria pollutants and evaluated them for mutagenicity in three Salmonella strains at the air-agar interface. We continuously injected into the chamber gasoline, nitric oxide, and ammonium sulfate, as well as either α-pinene to produce SA-PM, which had a high concentration of particulate matter (PM): 119 ppb ozone (O3), 321 ppb NO2, and 1007 µg/m3 PM2.5; or isoprene to produce SA-O3, which had a high ozone (O3) concentration: 415 ppb O3, 633 ppb NO2, and 55 µg/m3 PM2.5. Neither PM2.5 extracts, NO2, or O3 alone, nor nonphoto-oxidized mixtures were mutagenic or cytotoxic. Both photo-oxidized atmospheres were largely direct-acting base-substitution mutagens with similar mutagenic potencies in TA100 and TA104. The mutagenic potencies [(revertants/h)/(mgC/m3)] of SA-PM (4.3 ± 0.4) and SA-O3 (9.5 ± 1.3) in TA100 were significantly different ( P < 0.0001), but the mutation spectra were not ( P = 0.16), being ∼54% C → T and ∼46% C → A. Thus, the AQHI may have some predictive value for the mutagenicity of the gas phase of air.

Generation and characterization of diesel engine combustion emissions from petroleum diesel and soybean biodiesel fuels and application for inhalation exposure studies.

Biodiesel made from the transesterification of plant- and animal-derived oils is an important alternative fuel source for diesel engines. Although numerous studies have reported health effects associated with petroleum diesel emissions, information on biodiesel emissions are more limited. To this end, a program at the U.S. EPA assessed health effects of biodiesel emissions in rodent inhalation models. Commercially obtained soybean biodiesel (B100) and a 20% blend with petroleum diesel (B20) were compared to pure petroleum diesel (B0). Rats and mice were exposed independently for 4 h/day, 5 days/week for up to 6 weeks. Exposures were controlled by dilution air to obtain low (50 µg/m(3)), medium (150 µg/m(3)) and high (500 µg/m(3)) diesel particulate mass (PM) concentrations, and compared to filtered air. This article provides details on facilities, fuels, operating conditions, emission factors and physico-chemical characteristics of the emissions used for inhalation exposures and in vitro studies. Initial engine exhaust PM concentrations for the B100 fuel (19.7 ± 0.7 mg/m(3)) were 30% lower than those of the B0 fuel (28.0 ± 1.5 mg/m(3)). When emissions were diluted with air to control equivalent PM mass concentrations, B0 exposures had higher CO and slightly lower NO concentrations than B100. Organic/elemental carbon ratios and oxygenated methyl esters and organic acids were higher for the B100 than B0. Both the B0 and B100 fuels produced unimodal-accumulation mode particle-size distributions, with B0 producing lower concentrations of slightly larger particles. Subsequent papers in this series will describe the effects of these atmospheres on cardiopulmonary responses and in vitro genotoxicity studies.

The effects of B0, B20, and B100 soy biodiesel exhaust on aconitine-induced cardiac arrhythmia in spontaneously hypertensive rats.

CONTEXT: Diesel exhaust (DE) has been shown to increase the risk of cardiac arrhythmias. Although biodiesel has been proposed as a "safer" alternative to diesel, it is still uncertain whether it actually poses less threat. OBJECTIVE: We hypothesized that exposure to pure or 20% soy biodiesel exhaust (BDE) would cause less sensitivity to aconitine-induced arrhythmia than DE in rats. METHODS: Spontaneously hypertensive (SH) rats implanted with radiotelemeters were exposed once or for 5 d (4 h) to either 50 mg/m(3) (low), 150 mg/m(3) (medium), or 500 mg/m(3) (high) of DE (B0), 20% (B20) or 100% (B100) soy biodiesel exhaust. Arrhythmogenesis was assessed 24 h later by continuous infusion of aconitine, an arrhythmogenic drug, while heart rate (HR), and electrocardiogram (ECG) were monitored. RESULTS: Rats exposed once or for 5 d to low, medium, or high B0 developed arrhythmia at significantly lower doses of aconitine than controls, whereas rats exposed to B20 were only consistently sensitive after 5 d of the high concentration. B100 caused mild arrhythmia sensitivity at the low concentration, only after 5 d of exposure at the medium concentration and after either a single or 5 d at the high concentration. DISCUSSION AND CONCLUSIONS: These data demonstrate that exposure to B20 causes less sensitivity to arrhythmia than B0 and B100. This diminished effect may be due to lower irritant components such as acrolein and nitrogen oxides. Thus, in terms of cardiac health, B20 may be a safer option than both of the pure forms.

Comparative cardiopulmonary toxicity of exhausts from soy-based biofuels and diesel in healthy and hypertensive rats.

Increased use of renewable energy sources raise concerns about health effects of new emissions. We analyzed relative cardiopulmonary health effects of exhausts from (1) 100% soy biofuel (B100), (2) 20% soy biofuel + 80% low sulfur petroleum diesel (B20), and (3) 100% petroleum diesel (B0) in rats. Normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats were exposed to these three exhausts at 0, 50, 150 and 500 µg/m(3), 4 h/day for 2 days or 4 weeks (5 days/week). In addition, WKY rats were exposed for 1 day and responses were analyzed 0 h, 1 day or 4 days later for time-course assessment. Hematological parameters, in vitro platelet aggregation, bronchoalveolar lavage fluid (BALF) markers of pulmonary injury and inflammation, ex vivo aortic ring constriction, heart and aorta mRNA markers of vasoconstriction, thrombosis and atherogenesis were analyzed. The presence of pigmented macrophages in the lung alveoli was clearly evident with all three exhausts without apparent pathology. Overall, exposure to all three exhausts produced only modest effects in most endpoints analyzed in both strains. BALF γ-glutamyl transferase (GGT) activity was the most consistent marker and was increased in both strains, primarily with B0 (B0 > B100 > B20). This increase was associated with only modest increases in BALF neutrophils. Small and very acute increases occurred in aorta mRNA markers of vasoconstriction and thrombosis with B100 but not B0 in WKY rats. Our comparative evaluations show modest cardiovascular and pulmonary effects at low concentrations of all exhausts: B0 causing more pulmonary injury and B100 more acute vascular effects. BALF GGT activity could serve as a sensitive biomarker of inhaled pollutants.

Soy biodiesel emissions have reduced inflammatory effects compared to diesel emissions in healthy and allergic mice.

Toxicity of exhaust from combustion of petroleum diesel (B0), soy-based biodiesel (B100), or a 20% biodiesel/80% petrodiesel mix (B20) was compared in healthy and house dust mite (HDM)-allergic mice. Fuel emissions were diluted to target fine particulate matter (PM(2.5)) concentrations of 50, 150, or 500 µg/m(3). Studies in healthy mice showed greater levels of neutrophils and MIP-2 in bronchoalveolar lavage (BAL) fluid 2 h after a single 4-h exposure to B0 compared with mice exposed to B20 or B100. No consistent differences in BAL cells and biochemistry, or hematological parameters, were observed after 5 d or 4 weeks of exposure to any of the emissions. Air-exposed HDM-allergic mice had significantly increased responsiveness to methacholine aerosol challenge compared with non-allergic mice. Exposure to any of the emissions for 4 weeks did not further increase responsiveness in either non-allergic or HDM-allergic mice, and few parameters of allergic inflammation in BAL fluid were altered. Lung and nasal pathology were not significantly different among B0-, B20-, or B100-exposed groups. In HDM-allergic mice, exposure to B0, but not B20 or B100, significantly increased resting peribronchiolar lymph node cell proliferation and production of T(H)2 cytokines (IL-4, IL-5, and IL-13) and IL-17 in comparison with air-exposed allergic mice. These results suggest that diesel exhaust at a relatively high concentration (500 µg/m(3)) can induce inflammation acutely in healthy mice and exacerbate some components of allergic responses, while comparable concentrations of B20 or B100 soy biodiesel fuels did not elicit responses different from those caused by air exposure alone.

Health effects of soy-biodiesel emissions: mutagenicity-emission factors.

CONTEXT: Soy biodiesel is the predominant biodiesel fuel used in the USA, but only a few, frequently conflicting studies have examined the potential health effects of its emissions. OBJECTIVE: We combusted petroleum diesel (B0) and fuels with increasing percentages of soy methyl esters (B20, B50 and B100) and determined the mutagenicity-emission factors expressed as revertants/megajoule of thermal energy consumed (rev/MJ(th)). MATERIALS AND METHODS: We combusted each fuel in replicate in a small (4.3-kW) diesel engine without emission controls at a constant load, extracted organics from the particles with dichloromethane, determined the percentage of extractable organic material (EOM), and evaluated these extracts for mutagenicity in 16 strains/S9 combinations of Salmonella. RESULTS: Mutagenic potencies of the EOM did not differ significantly between replicate experiments for B0 and B100 but did for B20 and B50. B0 had the highest rev/MJ(th), and those of B20 and B100 were 50% and ∼85% lower, respectively, in strains that detect mutagenicity due to polycyclic aromatic hydrocarbons (PAHs), nitroarenes, aromatic amines or oxidative mutagens. For all strains, the rev/MJ(th) decreased with increasing biodiesel in the fuel. The emission factor for the 16 EPA Priority PAHs correlated strongly (r(2 )= 0.69) with the mutagenicity-emission factor in strain TA100 + S9, which detects PAHs. CONCLUSIONS: Under a constant load, soy-biodiesel emissions were 50-85% less mutagenic than those of petroleum diesel. Without additional emission controls, petroleum and biodiesel fuels had mutagenicity-emission factors between those of large utility-scale combustors (e.g. natural gas, coal, or oil) and inefficient open-burning (e.g. residential wood fireplaces).

Diesel exhaust induced pulmonary and cardiovascular impairment: the role of hypertension intervention.

Exposure to diesel exhaust (DE) and associated gases is linked to cardiovascular impairments; however, the susceptibility of hypertensive individuals is poorly understood. The objectives of this study were (1) to determine cardiopulmonary effects of gas-phase versus whole-DE and (2) to examine the contribution of systemic hypertension in pulmonary and cardiovascular effects. Male Wistar Kyoto (WKY) rats were treated with hydralazine to reduce blood pressure (BP) or l-NAME to increase BP. Spontaneously hypertensive (SH) rats were treated with hydralazine to reduce BP. Control and drug-pretreated rats were exposed to air, particle-filtered exhaust (gas), or whole DE (1500µg/m(3)), 4h/day for 2days or 5days/week for 4weeks. Acute and 4-week gas and DE exposures increased neutrophils and γ-glutamyl transferase (γ-GT) activity in lavage fluid of WKY and SH rats. DE (4weeks) caused pulmonary albumin leakage and inflammation in SH rats. Two-day DE increased serum fatty acid binding protein-3 (FABP-3) in WKY. Marked increases occurred in aortic mRNA after 4-week DE in SH (eNOS, TF, tPA, TNF-α, MMP-2, RAGE, and HMGB-1). Hydralazine decreased BP in SH while l-NAME tended to increase BP in WKY; however, neither changed inflammation nor BALF γ-GT. DE-induced and baseline BALF albumin leakage was reduced by hydralazine in SH rats and increased by l-NAME in WKY rats. Hydralazine pretreatment reversed DE-induced TF, tPA, TNF-α, and MMP-2 expression but not eNOS, RAGE, and HMGB-1. ET-1 was decreased by HYD. In conclusion, antihypertensive drug treatment reduces gas and DE-induced pulmonary protein leakage and expression of vascular atherogenic markers.

Oxidative stress, inflammatory biomarkers, and toxicity in mouse lung and liver after inhalation exposure to 100% biodiesel or petroleum diesel emissions.

Over the past decade, soy biodiesel (BD) has become a first alternative energy source that is economically viable and meets requirements of the Clean Air Act. Due to lower mass emissions and reduced hazardous compounds compared to diesel combustion emissions (CE), BD exposure is proposed to produce fewer adverse health effects. However, considering the broad use of BD and its blends in different industries, this assertion needs to be supported and validated by mechanistic and toxicological data. Here, adverse effects were compared in lungs and liver of BALB/cJ mice after inhalation exposure (0, 50, 150, or 500 µg/m3; 4 h/d, 5 d/wk, for 4 wk) to CE from 100% biodiesel (B100) and diesel (D100). Compared to D100, B100 CE produced a significant accumulation of oxidatively modified proteins (carbonyls), an increase in 4-hydroxynonenal (4-HNE), a reduction of protein thiols, a depletion of antioxidant gluthatione (GSH), a dose-related rise in the levels of biomarkers of tissue damage (lactate dehydrogenase, LDH) in lungs, and inflammation (myeloperoxidase, MPO) in both lungs and liver. Significant differences in the levels of inflammatory cytokines interleukin (IL)-6, IL-10, IL-12p70, monocyte chemoattractant protein (MCP)-1, interferon (IFN) γ, and tumor necrosis factor (TNF)-α were detected in lungs and liver upon B100 and D100 CE exposures. Overall, the tissue damage, oxidative stress, inflammation, and cytokine response were more pronounced in mice exposed to BD CE. Further studies are required to understand what combustion products in BD CE accelerate oxidative and inflammatory responses.

Cardiovascular and thermoregulatory responses of unrestrained rats exposed to filtered or unfiltered diesel exhaust.

Diesel exhaust has been associated with adverse cardiovascular and pulmonary health effects. The relative contributions of the gas phase and particulate components of diesel exhaust are less well understood. We exposed telemetered Wistar-Kyoto rats to air or diesel exhaust that was either filtered (F) or unfiltered [gas-phase plus diesel exhaust particles (DEP)], containing ~1.9 mg/m³ of particulate matter for 5 h/day; 5 days/week for 4 consecutive weeks. Blood pressure (BP), core temperature (T(c)), heart rate (HR), and cardiac contractility (CC) estimated by the QA interval were monitored by radiotelemetry during exposure as well as during a 2-week period of recovery. Pulmonary injury and inflammation markers were analysed after 2-day, and 4 weeks of exposure, and 2-week recovery. Exposure to F or DEP was associated with a trend for a reduction in BP during weeks 1, 2 and 4. A reduction in HR in the DEP group was apparent during week 4. Exposure to DEP but not F was associated with significant reduction in CC over weeks 1-4. There was also a slight elevation in T(c) during DEP exposure. All telemetry parameters were normal during recovery at night and a 2-week recovery period. Neutrophilic inflammation in bronchoalveolar lavage fluid was evident after 2 days and 4 weeks of exposure to F and DEP. There were no signs of inflammation after 2-week recovery. We found a significant decrease in CC and slight reduction in BP. Exposure to DEP and F is associated with pulmonary inflammation, and mild effects on HR, BP, and T(c) but there is a marked effect of DEP on CC.

Role of oxidative stress on diesel-enhanced influenza infection in mice.

Numerous studies have shown that air pollutants, including diesel exhaust (DE), reduce host defenses, resulting in decreased resistance to respiratory infections. This study sought to determine if DE exposure could affect the severity of an ongoing influenza infection in mice, and examine if this could be modulated with antioxidants. BALB/c mice were treated by oropharyngeal aspiration with 50 plaque forming units of influenza A/HongKong/8/68 and immediately exposed to air or 0.5 mg/m3 DE (4 hrs/day, 14 days). Mice were necropsied on days 1, 4, 8 and 14 post-infection and lungs were assessed for virus titers, lung inflammation, immune cytokine expression and pulmonary responsiveness (PR) to inhaled methacholine. Exposure to DE during the course of infection caused an increase in viral titers at days 4 and 8 post-infection, which was associated with increased neutrophils and protein in the BAL, and an early increase in PR. Increased virus load was not caused by decreased interferon levels, since IFN-ß levels were enhanced in these mice. Expression and production of IL-4 was significantly increased on day 1 and 4 p.i. while expression of the Th1 cytokines, IFN-γ and IL-12p40 was decreased. Treatment with the antioxidant N-acetylcysteine did not affect diesel-enhanced virus titers but blocked the DE-induced changes in cytokine profiles and lung inflammation. We conclude that exposure to DE during an influenza infection polarizes the local immune responses to an IL-4 dominated profile in association with increased viral disease, and some aspects of this effect can be reversed with antioxidants.

Mutagenicity emission factors of canola oil and waste vegetable oil biodiesel: Comparison to soy biodiesel.

Canola (or rapeseed) oil and waste vegetable oil (WVO) are used commonly to make biodiesel fuels composed completely from these oils (B100) or as blends with petroleum diesel (B0). However, no studies have reported the mutagenic potencies of the particulate matter with diameter ≤2.5 µm (PM2.5) or the mutagenicity emission factors, such as revertants/MJthermal (rev/MJth) for these biodiesel emissions. Using strains TA98 and TA100 with the Salmonella (Ames) mutagenicity assay, we determined these metrics for organic extracts of PM2.5 of emissions from biodiesel containing 5% soy oil (soy B5); 5, 20, 50, and 100% canola (canola B5, B20, B50, B100), and 100% waste vegetable oil (WVO B100). The mutagenic potencies (rev/mg PM2.5) of the canola B100 and WVO B100 emissions were generally greater than those of B0, whereas the mutagenicity emission factors (rev/MJth, rev/kg fuel, and rev/m3) were less, reflecting the lower PM emissions of the biodiesels relative to B0. Nearly all the rev/mg PM2.5 and rev/MJth values were greater in TA98 with S9 than without S9, indicating a relatively greater role for polycyclic aromatic hydrocarbons, which require S9, than nitroarenes, which do not. In TA100 -S9, the rev/mg PM2.5 and rev/MJth for the biodiesels were generally ≥ to those of B0, indicating that most of these biodiesels produced more direct-acting, base-substitution mutagenic activity than did B0. For B100 biodiesels and petroleum diesel, the rev/MJth in TA98 + S9 ranked: petroleum diesel > canola > WVO > soy. The diesel emissions generally had rev/MJth values orders of magnitude higher than those of large utility-scale combustors (natural gas, coal, oil, or wood) but orders of magnitude lower than those of inefficient open burning (e.g., residential wood fireplaces). These comparative data of the potential health effects of a variety of biodiesel fuels will help inform the life-cycle assessment and use of biodiesel fuels.