Long-term ambient ozone, omega-3 fatty acid, genetic susceptibility, and risk of mental disorders among middle-aged and older adults in UK biobank.

BACKGROUND: Evidence linking ozone to depression and anxiety disorders remains sparse and results are heterogeneous. It remains unknown whether omega-3 fatty acid, or genetic susceptibility of mental disorders modify the impacts of ozone. The aim is to assess the associations of ambient ozone with depression and anxiety, and further explore the potential modification effects of omega-3 fatty acid and genetic susceptibility. METHODS: In total of 257,534 participants were enrolled from 2006 to 2010 and followed up to 2016. Depression and anxiety were assessed using mental health questionnaires, primary care records and hospital admission records. The annual average concentrations of ozone were calculated and linked to individuals by home address. Dietary intake and plasma concentration were selected to reflect levels of omega-3 fatty acid. Polygenetic risk scores were selected to reflect genetic susceptibility. We examined the associations of ozone and incident mental disorders, and potential modification of omega-3 fatty acid and genetic susceptibility. RESULTS: Incidences of depression (N = 6957) and anxiety (N = 6944) was associated with increase of ozone. Higher levels of omega-3 fatty acid might attenuate the ozone related depression risk. However, the modification effects of genetic susceptibility were not found. CONCLUSIONS: Long-term exposure to ambient ozone increase the risk of mental disorders among the middle aged and older adults, and omega-3 fatty acid could reduce the adverse effects of ozone on mental health. Higher intake of omega-3 fatty acid is a potential strategy to prevent the risks caused by ozone on public mental health.

Elevated ozone effects on potato leaf physiology, growth, and yield: a meta-analysis.

Potato is an important crop worldwide and threatened by various environmental stresses, including elevated ozone (e[O3]). Here, we conducted a meta-analysis to quantify the effect of e[O3] on potato plants and how it varies depending upon different experimental conditions. Regarding plant growth and biomass, e[O3] significantly decreased shoot biomass by 18% and belowground biomass by 35%, while it increased the leaf area index by 19% and total number of injured leaves by 146%. As for yield, e[O3] significantly decreased the total tuber number by 21%. A relatively pronounced effect of e[O3] on the stomatal conductance was observed when exposure lasted 31-60 days, which was significantly greater than that after exposure lasted 96-311 days. The overall quantity of leaves was mainly decreased by higher (100-150 ppb) than lower (30-80 ppb) concentrations of e[O3] compared to ambient O3. The effect of e[O3] on the total tuber number was significant mainly when exposure lasted 31-90 days and was greater in plants grown in growth chambers than those planted in open-top chambers and glasshouses. The effect of e[O3] stress on physiology, growth, and yield varied among cultivars, with some cultivars showing marked tolerance relative to other cultivars. The findings can guide strategies to manage the negative impacts of e[O3] stress on potato production.

Uptake of ozone by allergenic pollen grains.

Ozone exacerbates allergy symptoms to certain pollens. The molecular mechanisms by which ozone affects pollen grains (PGs) and allergies are not fully understood, especially as the effects of pollutants may vary depending on the type of pollen. In this work, pollens of 22 different taxa were exposed under laboratory conditions to ozone (100 ppb) to quantify the ozone uptake by the PGs. The ozone uptake was highly variable among the 22 taxa tested. The highest ozone uptake per PG was measured on Acer negundo PGs (2.5 ± 0.2 pg∙PG-1). On average, tree pollens captured significantly more ozone than herbaceous pollens (average values of 0.5 and 0.02 pg∙PG-1, respectively). No single parameter (such as the number of apertures, pollen season, pollen size, or lipid fraction) could predict a pollen's ability to take up ozone. Lipids seem to act as a barrier to ozone uptake and play a protective role for some taxa. After inhalation of PGs, pollen-transported ozone could be transferred to mucous membranes and exacerbate symptoms through oxidative stress and local inflammation. Although the amount of ozone transported is small in absolute terms, it is significant compared to the antioxidant capacity of nasal mucus at a microscale. This mechanism of pollen-induced oxidative stress could explain the aggravation of allergic symptoms during ozone pollution episodes.

Acute Ozone-Induced Transcriptional Changes in Markers of Oxidative Stress and Glucocorticoid Signaling in the Rat Hippocampus and Hypothalamus Are Sex-Specific.

Exposure to a prototypic air pollutant ozone (O3) has been associated with the activation of neuroendocrine stress response along with neural changes in oxidative stress (OS), inflammation, and Alzheimer's disease-like pathologies in susceptible animal models. We hypothesized that neural oxidative and transcriptional changes induced by O3 in stress responsive regions are sex-dependent. Male and female adult Long-Evans rats were exposed to filtered air or O3 for two consecutive days (0.8 ppm, 4 h/day) and brain regions were flash-frozen. Activities of cerebellar OS parameters and mitochondrial complex I, II, and IV enzymes were assessed to confirm prior findings. We assessed transcriptional changes in hypothalamus (HYP) and hippocampus (HIP) for markers of OS, microglial activity and glucocorticoid signaling using qPCR. Although there were no O3 or sex-related differences in the cerebellar activities of OS and mitochondrial enzymes, the levels of protein carbonyls and complex II activities were higher in females regardless of O3. There were no statistical differences in baseline expression of genes related to OS (Cat, Dhcr24, Foxm1, Gpx1, Gss, Nfe2l2, Sod1) except for lower HYP Sod1 expression in air-exposed females than males, and higher HIP Gss expression in O3-exposed females relative to matched males. Microglial marker Aif1 expression was higher in O3-exposed females relative to males; O3 inhibited Itgam only in males. The expression of Bdnf in HIP and HYP was inhibited by O3 in both sexes. Genes related to glucocorticoid signaling (Fkbp4, Fkbp5, Hsp90aa1, Hspa4, nr3c1, nr3c2) showed sex-specific effects due to O3 exposure. Baseline expression of HIP Fkbp4 was higher in females relative to males. O3 inhibited Nr3c1 in female HIP and male HYP, but Nr3c2 was inhibited in male HYP. Fkbp4 expression was higher in O3-exposed females when compared to matched males, whereas Fkbp5 was expressed at higher levels in both brain regions of males and females. These results indicate that sex-specific brain region responses to O3 might, in part, be caused by OS and regulation of glucocorticoid signaling.

Personal ozone exposure and stress hormones in the hypothalamus-pituitary-adrenal and sympathetic-adrenal-medullary axes.

BACKGROUND: The effect of ozone exposure on neuroendocrine responses in humans has not been fully studied. METHODS: We conducted a longitudinal panel study with four rounds of visits among 43 college students in Shanghai, China, from May to October 2016. For each visit, we monitored personal real-time ozone exposure for consecutive 3 days (from 8:00 a.m. to 6:00p.m. each day), followed by blood sample collection. We measured serum levels of three hormones in the hypothalamus-pituitaryadrenal (HPA) axis, including corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol, and three catacholamines indicating sympathetic-adrenal-medullary (SAM) axis activation, including adrenaline, noradrenaline, and dopamine. We applied linear mixed-effect models to evaluate the associations between ozone exposure and these neurohormones and further compared models using personal and fixed-site ozone measurements. MAIN RESULTS: At lag 0-8 h, personal ozone exposure ranged from 4.5 ppb to 104.3 ppb with an average of 21.0 ± 14.7 ppb, which was approximately half of the ambient ozone concentration. Per 10-ppb increase in personal ozone exposure (lag 0-8 h) was associated with increases of 5.60% [95% confidence interval (CI): 2.30%, 9.01%] in CRH, 5.91% (95% CI: 0.55%, 11.56%) in cortisol, and 10.13% (95% CI: 2.75%, 18.05%) in noradrenaline, whereas associated with a 12.15% (95% CI: 1.23%, 21.87%) decrease in dopamine. Overall, models using personal ozone measurements yielded larger effect estimates and better model fits than models using fixed-site measurements. CONCLUSIONS: Short-term exposure to low levels of ozone may lead to activation of the HPA and SAM axes.

Maqui berry (Aristotelia chilensis) extract improves memory and decreases oxidative stress in male rat brain exposed to ozone.

Introduction: Prolonged ozone exposure can produce a state of oxidative stress, which in turn causes alterations in the dynamics of the brain and affects memory and learning. Moreover, different investigations have shown that high flavonoid content berries show a great antioxidant activity. The relationship between the protective effect of the maqui berry extract and its antioxidant properties in the brain has not been studied in depth. Objectives: The present study evaluated whether the protection exerted by the aqueous extract of maqui berry in brain regions associated with cognitive performance is due to its antioxidant capacity. Methods: Sprague Dawley rats were exposed to 0.25 ppm ozone and administered with maqui berry extracts. At the end of the treatments, spatial learning and short- and long-term memory were evaluated, as well as oxidative stress markers. Results: The administration of 50 and 100 mg/kg of the aqueous extract of maqui berry was effective in preventing the cognitive deficit caused by chronic exposure to ozone. The antioxidant effect of the administration of maqui berry was analyzed in the prefrontal cortex, hippocampus, and amygdala. Oxidative stress markers levels decreased and the enzymatic activity of superoxide dismutase diminished in animals exposed to ozone treated with the 50 mg/kg dose of maqui berry. Discussion: These results show a relationship between protection at the cognitive level and a decrease in oxidative stress markers, which suggests that the prevention of cognitive damage is due to the antioxidant activity of the maqui berry.

Ozone impairs the response of isoprene emission to foliar nitrogen and phosphorus in poplar.

Tropospheric ozone (O3) impairs physiological processes of plants while nitrogen (N) deposition may cause imbalances in soil N and other nutrients such as phosphorus (P) suggesting an increase of P demand for plants. However, the combined effect of O3, soil N and P on isoprene emission from leaves has never been tested. We therefore examined isoprene emission in leaves of Oxford poplar clone exposed to O3 (ambient, AA [35.0 nmol mol-1 as daily mean]; 1.5 × AA; 2.0 × AA), soil N (0 and 80 kg N ha-1) and soil P (0, 40 and 80 kg P ha-1) in July and September in a Free-Air Controlled Exposure (FACE) facility. We also investigated the response of isoprene emission to foliar N, P and abscisic acid (ABA) contents in September because the 2-C-methylerythritol-5-phosphate (MEP) pathway of isoprenoid biosynthesis produces ABA. We found that O3 increased isoprene emission in July, which was associated to increased dark respiration, suggesting an activation of metabolism against O3 stress as an initial response. However, O3 decreased isoprene emission in September which was associated to reduced net photosynthesis. In September, isoprene emission was positively correlated with leaf N content and negatively correlated with leaf P content in AA. However, no response of isoprene emission to foliar N and P was found in elevated O3, suggesting that the isoprene responses to foliar N and P depended on the O3 exposure levels. Isoprene emission rate in 1.5 × AA and 2.0 × AA increased with increasing leaf ABA content, indicating accelerated senescence of injured leaves to favor new leaf growth when high O3 and nutritional availability in the soil were combined. Even though foliar N and P usually act as a proxy for isoprene emission rate, the impact of recent abiotic factors such as O3 should be always considered for modeling isoprene emission under climate change.

Effects of ozone on agriculture, forests and grasslands.

The damage and injury that ground level ozone (O3) causes vegetation has become increasingly evident over the past half century with a large body of observational and experimental evidence demonstrating a variety of effects at ambient concentrations on crop, forest and grassland species and ecosystems. This paper explores the use of experimental data to develop exposure-response relationships for use in risk assessment studies. These studies have typically identified the USA mid-West, much of Europe, the Indo Gangetic Plain in South Asia and the Eastern coastal region of China as global regions where O3 is likely to threaten food supply and other ecosystems. Global risk assessment modelling estimates yield losses of staple crops between 3 to 16% causing economic losses of between US$14 to 26 billion in the year 2000. Changes in anthropogenic emissions of O3 precursors in recent decades have modified O3 concentration profiles (peaks versus background O3) and global distributions with the Northern Hemisphere seeing increases in O3 levels of between 1 and 5 ppb/decade since the 1950s and the emergence of Asia as the region with the highest O3 concentrations. In the future, O3 mitigation could focus on methane (CH4) and nitrogen oxide (NOx) emissions; these will differentially influence global and local/regional O3 concentrations and influence daily and seasonal profiles. The consequent effects on vegetation will in part depend on how these changes in O3 profile alter the exceedance of detoxification thresholds for plant damage. Adaptation options may play an important role in enhancing food supply while mitigation strategies are being implemented. An improved understanding of the mechanisms by which O3 affects plants, and how this might influence detoxification thresholds and interactions with other environmental variables such as water stress and nutrients, would help develop O3 deposition and impact models to support the development of crop, land-surface exchange and ultimately earth system models for holistic assessments of global change. This article is part of a discussion meeting issue 'Air quality, past present and future'.

The effects of ozone exposure and sedentary lifestyle on neuronal microglia and mitochondrial bioenergetics of female Long-Evans rats.

Ozone (O3) is a widespread air pollutant that produces cardiovascular and pulmonary dysfunction possibly mediated by activation of central stress centers. Epidemiological data suggest that sedentary lifestyles may exacerbate responses to air pollutants such as O3. We sought to assess neurological changes in response to O3 exposure and an active lifestyle. We developed an animal model in which female Long-Evans rats were either sedentary or active with continuous access to running wheels starting at postnatal day (PND) 22 until the age of PND 100 and then exposed to O3 (0, 0.25, 0.5 or 1.0 ppm) 5 h/day for two consecutive days. We found significantly more reactive microglia within the hippocampus (HIP) in animals exposed to O3 in both sedentary and active rats. No changes were detected in astrocytic coverage. We next analyzed mitochondrial bioenergetic parameters (complex I, complex II and complex IV). Complex I activity was significantly affected by exercise in hypothalamus (HYP). Complex II activity was significantly affected by both exercise and O3 exposure in the HIP. Concomitant with the changes in enzymatic activity, there were also effects on expression of genes related to mitochondrial bioenergetics and antioxidant production. These results demonstrate that O3 induces microglia reactivity within stress centers of the brain and that mitochondrial bioenergetics are altered. Some of these effects may be augmented by exercise, suggesting a role for lifestyle in O3 effects on brain mitochondrial bioenergetics parameters in agreement with our previous reports on other endpoints.

Blueberry Extracts as a Novel Approach to Prevent Ozone-Induced Cutaneous Inflammasome Activation.

The World Health Organization estimates that 7 million people die every year due to pollution exposure. Among the different pollutants to which living organism are exposed, ozone (O3) represents one of the most toxic, because its location which is the skin is one of the direct tissues exposed to the outdoor environment. Chronic exposure to outdoor stressors can alter cutaneous redox state resulting in the activation of inflammatory pathways. Recently, a new player in the inflammation mechanism was discovered: the multiprotein complex NLRP1 inflammasome, which has been shown to be also expressed in the skin. The topical application of natural compounds has been studied for the last 40 years as a possible approach to prevent and eventually cure skin conditions. Recently, the possibility to use blueberry (BB) extract to prevent pollution-induced skin toxicity has been of great interest in the cosmeceutical industry. In the present study, we analyzed the cutaneous protective effect of BB extract in several skin models (2D, 3D, and human skin explants). Specifically, we observed that in the different skin models used, BB extracts were able to enhance keratinocyte wound closure and normalize proliferation and migration responses previously altered by O3. In addition, pretreatment with BB extracts was able to prevent ozone-induced ROS production and inflammasome activation measured as NRLP1-ASC scaffold formation and also prevent the transcripts of key inflammasome players such as CASP1 and IL-18, suggesting that this approach as a possible new technology to prevent cutaneous pollution damage. Our data support the hypothesis that BB extracts can effectively reduce skin inflammation and be a possible new technology against cutaneous pollution-induced damage.

Endogenous melatonin mediation of systemic inflammatory responses to ozone exposure in healthy adults.

BACKGROUND/AIM: Melatonin is a free radical scavenger and an anti-inflammatory biomolecule. Air pollution exposure has been associated with increased inflammatory responses. We hypothesize that endogenous melatonin plays a role in inflammatory responses to air pollution exposure. METHODS: We tested this hypothesis in a cohort of 53 healthy adults (22-52 years old, 16 women), none of whom were on melatonin supplementation. Early morning urine and fasting blood were collected from each participant longitudinally up to three times. We analyzed urinary 6-sulfatoxymelatonin (aMT6s), as a surrogate of circulating melatonin, and pro- and anti-inflammatory cytokines in the plasma samples. Indoor and outdoor air pollutants were measured and combined with participants' time-activity patterns to calculate personal exposure to O3, PM2.5, NO2, and SO2 averaged over 12-hour, 24-hour, 1-week, and 2-week periods prior to biospecimen collection, respectively. Linear mixed-effects models were used to examine the relationships among urinary aMT6s, personal pollutant exposure, and plasma cytokines. A mediation analysis was conducted to examine the role of aMT6s in the relationships between pollutant exposures and inflammatory cytokines. RESULTS: One interquartile range (4.2 ppb) increase in 2-week O3 exposure was associated with a -26.2% (95% CI: -43.9% to -2.8%) decrease in aMT6s. Within the range of endogenous aMT6s concentrations (0.5-53.0 ng/ng creatinine) across the participants, increased aMT6s was associated with decreased pro-inflammatory cytokines including IL-1ß, IL-8, IL-17A, IFN-γ, and TNF-α. These cytokines were significantly and positively associated with 2-week average O3 exposure. Furthermore, 7.4% to 17.4% of the O3-cytokine associations were mediated by aMT6s. We did not find similar effects for the other pollutants. CONCLUSIONS: Pro-inflammatory responses to O3 exposure in the preceding 2 weeks partly resulted from the depletion of endogenous melatonin by O3.

Supplementation with omega-3 fatty acids potentiates oxidative stress in human airway epithelial cells exposed to ozone.

BACKGROUND: Dietary intake of the omega-3 family of polyunsaturated fatty acids (ω-3 FA) is associated with anti-inflammatory effects. However, unsaturated fatty acids are susceptible to oxidation, which produces pro-inflammatory mediators. Ozone (O3) is a tropospheric pollutant that reacts rapidly with unsaturated fatty acids to produce electrophilic and oxidative mediators of inflammation. OBJECTIVE: Determine whether supplementation with ω-3 FA alters O3-induced oxidative stress in human airway epithelial cells (HAEC). METHODS: 16-HBE cells expressing a genetically encoded sensor of the reduced to oxidized glutathione ratio (GSH/GSSG, EGSH) were supplemented with saturated, monounsaturated, or ω-3 FA prior to exposure to 0, 0.08, 0.1, or 0.3 ppm O3. Lipid peroxidation was measured in cellular lipid extracts and intact cells following O3 exposure. RESULTS: Relative to cells incubated with the saturated or monounsaturated fatty acids, cells supplemented with ω-3 FA containing 5 or 6 double bonds showed a marked increase in EGSH during exposure to O3 concentrations as low as 0.08 ppm. Consistent with this finding, the concentration of lipid hydroperoxides produced following O3 exposure was significantly elevated in ω-3 FA supplemented cells. DISCUSSION: Supplementation with polyunsaturated ω-3 FA potentiates oxidative responses, as indicated by EGSH, in HAEC exposed to environmentally relevant concentrations of O3. This effect is mediated by the increased formation of lipid hydroperoxides produced by the reaction of O3 with polyunsaturated fatty acids. Given the inflammatory activity of lipid hydroperoxides, these findings have implications for the potential role of ω-3 FA in increasing human susceptibility to the adverse health effects of O3 exposure.

Alleviated systemic oxidative stress effects of combined atmospheric oxidant capacity by fish oil supplementation: A randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Combined atmospheric oxidant capacity (Ox), represented by the sum of nitrogen dioxide (NO2) and ozone (O3), is an important hazardous property of outdoor air pollution mixture. It remains unknown whether its adverse effects can be ameliorated by dietary fish-oil supplementation. OBJECTIVE: To assess the effects of fish-oil supplementation against oxidative stress induced by acute Ox exposure. METHODS: We conducted a randomized, double-blinded and placebo-controlled study among 65 young adults in Shanghai, China between September 2017 and January 2018. We randomly assigned participants to receive either 2.5 g/day of fish oil or placebo, and conducted four repeated physical examinations during the last two months of treatments. Ox concentrations were calculated as the sum of hourly measurements of NO2 and O3. We measured six biomarkers on systemic oxidative stress and antioxidant activity. Linear mixed-effect models were used to assess the short-term effects of Ox on biomarkers in each group. RESULTS: During our study period, the 72-h average Ox concentration was 93.6 µg/m3. Short-term exposure to Ox led to weaker changes in all biomarkers in the fish oil group than in the placebo group. Compared with the placebo group, for a 10-µg/m3 increase in Ox, there were smaller decrements in myeloperoxidase (MPO, difference = 5.92%, lag = 0-2 d, p = 0.03) and malondialdehyde (MDA, difference = 5.00%, lag = 1 d, p = 0.04) in the fish-oil group; there were also larger increments in total antioxidant capacity (TAC, difference = 16.33%, lag = 2 d, p = 0.02) and in glutathione peroxidase (GSH-Px, difference = 8.89%, lag = 0-2 d, p = 0.03) in the fish-oil group. The estimated differences for MPO were robust to adjustment for all co-pollutants and the differences for other biomarkers remained for some co-pollutants. CONCLUSIONS: This trial provides first-hand evidence that dietary fish-oil supplementation may alleviate the systemic oxidative stress induced by Ox.

Microbiota Contribute to Obesity-related Increases in the Pulmonary Response to Ozone.

Obesity is a risk factor for asthma, especially nonatopic asthma, and attenuates the efficacy of standard asthma therapeutics. Obesity also augments pulmonary responses to ozone, a nonatopic asthma trigger. The purpose of this study was to determine whether obesity-related alterations in gut microbiota contribute to these augmented responses to ozone. Ozone-induced increases in airway responsiveness, a canonical feature of asthma, were greater in obese db/db mice than in lean wild-type control mice. Depletion of gut microbiota with a cocktail of antibiotics attenuated obesity-related increases in the response to ozone, indicating a role for microbiota. Moreover, ozone-induced airway hyperresponsiveness was greater in germ-free mice that had been reconstituted with colonic contents of db/db than in wild-type mice. In addition, compared with dietary supplementation with the nonfermentable fiber cellulose, dietary supplementation with the fermentable fiber pectin attenuated obesity-related increases in the pulmonary response to ozone, likely by reducing ozone-induced release of IL-17A. Our data indicate a role for microbiota in obesity-related increases in the response to an asthma trigger and suggest that microbiome-based therapies such as prebiotics may provide an alternative therapeutic strategy for obese patients with asthma.

Ozone risk assessment is affected by nutrient availability: Evidence from a simulation experiment under free air controlled exposure (FACE).

Assessing ozone (O3) risk to vegetation is crucial for informing policy making. Soil nitrogen (N) and phosphorus (P) availability could change stomatal conductance which is the main driver of O3 uptake into a leaf. In addition, the availability of N and P could influence photosynthesis and growth. We thus postulated that the sensitivity of plants to O3 may be changed by the levels of N and P in the soil. In this study, a sensitive poplar clone (Oxford) was subject to two N levels (N0, 0 kg N ha-1; N80, 80 kg N ha-1), three P levels (P0, 0 kg P ha-1; P40, 40 kg P ha-1; P80, 80 kg P ha-1) and three levels of O3 exposure (ambient concentration, AA; 1.5 × AA; 2.0 × AA) for a whole growing season in an O3 free air controlled exposure (FACE) facility. Flux-based (POD0 to 6) and exposure-based (W126 and AOT40) dose-response relationships were fitted and critical levels (CLs) were estimated for a 5% decrease of total annual biomass. It was found that N and P availability modified the dose-response relationships of biomass responses to O3. Overall, the N supply decreased the O3 CLs i.e. increased the sensitivity of poplar to O3. Phosphorus alleviated the O3-caused biomass loss and increased the CL. However, such mitigation effects of P were found only in low N and not in high N conditions. In each nutritional treatment, similar performance was found between flux-based and exposure-based indices. However, the flux-based approach was superior, as compared to exposure indices, to explain the biomass reduction when all nutritional treatments were pooled together. The best O3 metric for risk assessments was POD4, with 4.6 mmol m-2 POD4 as a suitable CL for Oxford poplars grown under various soil N and P conditions.

Ozone-Induced Vascular Contractility and Pulmonary Injury Are Differentially Impacted by Diets Enriched With Coconut Oil, Fish Oil, and Olive Oil.

Fish, olive, and coconut oil dietary supplementation have several cardioprotective benefits, but it is not established if they protect against air pollution-induced adverse effects. We hypothesized that these dietary supplements would attenuate ozone-induced systemic and pulmonary effects. Male Wistar Kyoto rats were fed either a normal diet, or a diet supplemented with fish, olive, or coconut oil for 8 weeks. Animals were then exposed to air or ozone (0.8 ppm), 4 h/day for 2 days. Ozone exposure increased phenylephrine-induced aortic vasocontraction, which was completely abolished in rats fed the fish oil diet. Despite this cardioprotective effect, the fish oil diet increased baseline levels of bronchoalveolar lavage fluid (BALF) markers of lung injury and inflammation. Ozone-induced pulmonary injury/inflammation were comparable in rats on normal, coconut oil, and olive oil diets with altered expression of markers in animals fed the fish oil diet. Fish oil, regardless of exposure, led to enlarged, foamy macrophages in the BALF that coincided with decreased pulmonary mRNA expression of cholesterol transporters, cholesterol receptors, and nuclear receptors. Serum microRNA profile was assessed and demonstrated marked depletion of a variety of microRNAs in animals fed the fish oil diet, several of which were of splenic origin. No ozone-specific changes were noted. Collectively, these data indicate that although fish oil offered vascular protection from ozone exposure, it increased pulmonary injury/inflammation and impaired lipid transport mechanisms resulting in foamy macrophage accumulation, demonstrating the need to be cognizant of potential off-target pulmonary effects that might offset the overall benefit of this vasoprotective supplement.

Elevated ozone affects C, N and P ecological stoichiometry and nutrient resorption of two poplar clones.

The effects of elevated ozone on C (carbon), N (nitrogen) and P (phosphorus) ecological stoichiometry and nutrient resorption in different organs including leaves, stems and roots were investigated in poplar clones 546 (P. deltoides cv. '55/56' × P. deltoides cv. 'Imperial') and 107 (P. euramericana cv. '74/76') with a different sensitivity to ozone. Plants were exposed to two ozone treatments, NF (non-filtered ambient air) and NF60 (NF with targeted ozone addition of 60 ppb), for 96 days in open top chambers (OTCs). Significant ozone effects on most variables of C, N and P ecological stoichiometry were found except for the C concentration and the N/P in different organs. Elevated ozone increased both N and P concentrations of individual organs while for C/N and C/P ratios a reduction was observed. On these variables, ozone had a greater effect for clone 546 than for clone 107. N concentrations of different leaf positions ranked in the order upper > middle > lower, showing that N was transferred from the lower senescent leaves to the upper ones. This was also indicative of N resorption processes, which increased under elevated ozone. N resorption of clone 546 was 4 times larger than that of clone 107 under ambient air (NF). However, elevated ozone (NF60) had no significant effect on P resorption for both poplar clones, suggesting that their growth was only limited by N, while available P in the soil was enough to sustain growth. Understanding ecological stoichiometric responses under ozone stress is crucial to predict future effects on ecological processes and biogeochemical cycles.

Mechanisms of aging and development-A new understanding of environmental damage to the skin and prevention with topical antioxidants.

Recent research has given us new insights into the molecular biology of extrinsic aging of the skin. Not only does UV irradiation directly cause photoaging of the skin, but also environmental pollutants significantly damage exposed skin by several mechanisms. Exposure to the noxious gases of air pollution with simultaneous exposure to UVA can act synergistically to initiate skin cancer. Also ozone generated from pollutants reacting with UV induces oxidative stress of the skin's surface via formation of lipid peroxidation products, with cascading consequences to deeper layers. Furthermore, new studies have demonstrated that particulate matter (PM) pollutants can penetrate the skin transepidermally and through hair follicles to induce skin aging via the aryl hydrocarbon receptor (AHR), a recently discovered ligand-activated transcription factor that regulates and protects keratinocytes, melanocytes, and fibroblasts. With this understanding that extrinsic aging of the skin is not only due to photoaging, we realize the necessity of protection beyond sunscreen. Fortunately, correctly formulated topical antioxidants can prevent damage inflicted by both UV and environmental pollution.

Characterization of the Potent, Selective Nrf2 Activator, 3-(Pyridin-3-Ylsulfonyl)-5-(Trifluoromethyl)-2H-Chromen-2-One, in Cellular and In Vivo Models of Pulmonary Oxidative Stress.

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key regulator of oxidative stress and cellular repair and can be activated through inhibition of its cytoplasmic repressor, Kelch-like ECH-associated protein 1 (Keap1). Several small molecule disrupters of the Nrf2-Keap1 complex have recently been tested and/or approved for human therapeutic use but lack either potency or selectivity. The main goal of our work was to develop a potent, selective activator of NRF2 as protection against oxidative stress. In human bronchial epithelial cells, our Nrf2 activator, 3-(pyridin-3-ylsulfonyl)-5-(trifluoromethyl)-2H-chromen-2-one (PSTC), induced Nrf2 nuclear translocation, Nrf2-regulated gene expression, and downstream signaling events, including induction of NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme activity and heme oxygenase-1 protein expression, in an Nrf2-dependent manner. As a marker of subsequent functional activity, PSTC restored oxidant (tert-butyl hydroperoxide)-induced glutathione depletion. The compound's engagement of the Nrf2 signaling pathway translated to an in vivo setting, with induction of Nrf2-regulated gene expression and NQO1 enzyme activity, as well as restoration of oxidant (ozone)-induced glutathione depletion, occurring in the lungs of PSTC-treated rodents. Under disease conditions, PSTC engaged its target, inducing the expression of Nrf2-regulated genes in human bronchial epithelial cells derived from patients with chronic obstructive pulmonary disease, as well as in the lungs of cigarette smoke-exposed mice. Subsequent to the latter, a dose-dependent inhibition of cigarette smoke-induced pulmonary inflammation was observed. Finally, in contrast with bardoxolone methyl and sulforaphane, PSTC did not inhibit interleukin-1ß-induced nuclear factor-κB translocation or insulin-induced S6 phosphorylation in human cells, emphasizing the on-target activity of this compound. In summary, we characterize a potent, selective Nrf2 activator that offers protection against pulmonary oxidative stress in several cellular and in vivo models.