Inhalation Of Nitrogen Dioxide Research Articles

Estimating Inhaled Nitrogen Dioxide from the Human Biometric Response

Breathing clean air is crucial for maintaining good human health. The air we inhale can significantly impact our physical and mental well-being, influenced by parameters such as particulate matter and gases (e.g. carbon dioxide, carbon monoxide, and nitrogen dioxide). Building on previous research that explored the effects of particulate matter (PM) in specific environments, analyzed using biometric indicators and machine learning models; this work focuses on the effects and estimation of inhaled nitrogen dioxide (NO<sub>2</sub>). This study involved a cyclist equipped with sensors to monitor various biometric parameters. In addition, an electric car following the cyclist measured the ambient NO<sub>2</sub> levels using an onboard sensor. A total of 329 biometric variables have been taken into account, of which 320 biometric variables are cognitive responses extracted using an electroencephalogram (EEG) and 9 biometric variables are physiological responses extracted using several sensors. Inhaled NO<sub>2</sub> levels are first estimated initially by making use of all 329 variables, then using 9 physiological responses and finally using only 6 of the 9 physiological responses. The study also uses a ranking method to pinpoint which biometric variables most significantly estimate inhaled NO<sub>2</sub> levels. Furthermore, it investigates the linear and non-linear relationship between certain variables and inhaled NO<sub>2</sub>. The general precision of the prediction for the data set was moderate, as indicated by the coefficient of determination (R<sup>2</sup>) and the root mean square error (RMSE) between the true and estimated values of NO<sub>2</sub> to be 0.35 and 5.41 ppb, respectively, in the test set. A higher accuracy in the prediction of lower values of NO<sub>2</sub> levels was qualitatively observed using a scatter diagram and a Quantile-Quantile plot where the data were more plentiful. For more robust conclusions, additional data and refined machine learning models are necessary.

The potential role of nitrogen dioxide inhalation in Parkinson’s disease

The potential role of nitrogen dioxide inhalation in Parkinson’s disease

Acute chemical pulmonary edema with inhaled nitrogen dioxide intoxication

Nitrogen dioxide is released by the interaction of some metals with nitric acid. Inhalation intoxication with nitrogen dioxide leads to chemical pulmonary edema. This study presents the case of a patient who had acute inhalation exposure to an unidentified brown gaseous substance (presumably nitrogen dioxide) when he etched a metal product with nitric acid. Twenty-four hours after contact with the gas, he manifested signs of intoxication, such as chest pain, tachypnea, and decreased saturation. Laboratory tests revealed hemoconcentration, hyperfermentemia, and arterial hypoxemia. The X-ray image of the entire lung surface revealed a sharp increase and deformation of the pulmonary pattern due to the vascular component. The diagnosis was T65, i.e., toxic effect of other and unspecified substances. With treatment, the patients condition improved. On day 4 after therapeutic exposure, with decreased oxygen fraction in the inhaled gas mixture to 0.3, the saturation increased to 98%, and tachypnea disappeared. On day 6, with ongoing treatment (oxygen therapy, use of antioxidants, antihypoxants, anti-inflammatory, and antibacterial drugs), the inflammatory reaction stopped, the rheological properties of the blood improved, and the gas composition of arterial blood normalized, i.e., the oxygenation index was 436, which indicated the disappearance of arterial blood oxygenation disorders. During the radiological examination, the normal radiological picture of the lungs was determined. Thus, on day 6 after the start of therapy, signs of intoxication were completely stopped. Specific changes in the lungs during radiation research techniques, hemoconcentration, inflammation, and hypoxemia during laboratory blood tests should be considered prognostic signs of chemical pulmonary edema. As a pathogenetic therapy, treatment must be supplemented with drugs that stop the cascade of free radical oxidation reactions (acetylcysteine and sodium thiosulfate). Individuals exposed to nitrogen dioxide should be considered a high-risk group for lung damage and hospitalized for dynamic observation for at least 2 days. Taking into account the genotoxic effects of nitrogen dioxide, affected patients should be classified as at risk of developing neoplasms and undergo further dynamic monitoring.

Лечебная эффективность Н-холинолитика N,N-диэтил-5,5-дифенил-2-пентиниламина на моделях некардиогенного отека легких

The existing non-cardiogenic pulmonary edema (NCPE) treatment methods are not sufficiently effective. N,N-Diethyl-5,5-diphenyl-2-pentynylamine hydrochloride (DDPA), the N-cholinolitic drug, is of interest as a potential remedy for treatment of toxic pulmonary edema (TPE). The study was aimed to determine therapeutic efficacy of the drug in animal TPE models. TPE in white rats was induced through intraperitoneal thiourea injection or nitrogen dioxide inhalation. Treatment of animals involved inhalation of the DDPA aqueous solution. The efficacy was estimated based on the animals’ survival rate and lung gravimetry data. The results were assessed based on descriptive statistics using the Student's t-test. In the model of thiourea-induced NCPE, the drug administered after the toxic exposure increased the animals’ survival rate and significantly decreased lung hydration levels (149% vs. 262.5% in non-treated animals). In the model of nitrogen dioxideinduced NCPE, the drug significantly increased the rats’ survival rate within the period between 0 and 5 h, however, the differences became non-significant within 24 h. The treated animals had 15–20% lower respiratory rate and pulmonary coefficients than non-treated animals 5 h after the NO2 exposure. The use of DDPA improved the survival rate and overall health in both TPE models, however, the thiourea-based model showed better treatment outcomes compared to the NO2–based model. Such differences can be explained by the deeper and more disruptive nature of the lung tissue injury caused by nitrogen dioxide compared to that caused by thiourea. Thus, the use of DDPA in individuals with injuries induced by pulmonotoxic chemicals may be promising at the prehospital stage.

High-Dose Nitric Oxide From Pressurized Cylinders and Nitric Oxide Produced by an Electric Generator From Air.

High-dose (≥ 80 ppm) inhaled nitric oxide (INO) has antimicrobial effects. We designed a trial to test the preventive effects of high-dose NO on coronavirus disease 2019 (COVID-19) in health care providers working with patients with COVID-19. The study was interrupted prematurely due to the introduction of COVID-19 vaccines for health care professionals. We thereby present data on safety and feasibility of breathing 160 ppm NO using 2 different NO sources, namely pressurized nitrogen/NO cylinders (INO) and electric NO (eNO) generators. NO gas was inhaled at 160 ppm in air for 15 min twice daily, before and after each work shift, over 14 d by health care providers (NCT04312243). During NO administration, vital signs were continuously monitored. Safety was assessed by measuring transcutaneous methemoglobinemia (SpMet) and the inhaled nitrogen dioxide (NO2) concentration. Twelve healthy health care professionals received a collective total of 185 administrations of high-dose NO (160 ppm) for 15 min twice daily. One-hundred and seventy-one doses were delivered by INO and 14 doses by eNO. During NO administration, SpMet increased similarly in both groups (P = .82). Methemoglobin decreased in all subjects at 5 min after discontinuing NO administration. Inhaled NO2 concentrations remained between 0.70 ppm (0.63-0.79) and 0.75 ppm (0.67-0.83) in the INO group and between 0.74 ppm (0.68-0.78) and 0.88 ppm (0.70-0.93) in the eNO group. During NO administration, peripheral oxygen saturation and heart rate did not change. No adverse events occurred. This pilot study testing high-dose INO (160 ppm) for 15 min twice daily using eNO seems feasible and similarly safe when compared with INO.

Dilatation Reserve of Pulmonary Arteries at Stages of the Chronic Obstructive Pulmonary Disease Model.

To assess the state of pulmonary vascular mediator systems during the stepwise formation of the chronic obstructive pulmonary disease (COPD) model. The COPD model was induced in rats by nitrogen dioxide (NO2) inhalation for 60 days. At different stages of COPD (15, 30, and 60 days), the effect of reagents-vasodilators (β-adrenoceptor agonist isoproterenol, nitric oxide donor nitrosorbide, acetylcholine, activator of C-fibers capsaicin, corticosteroid beclometasone) on the isolated pulmonary arteries (diameter <0.5 mm) was studied. Vascular reactivity was assessed by determining isometric contraction (tension in milligrams) of arterial rings by using an electromechanical transducer. All vasodilators dose-dependently decreased the vascular tone of pulmonary arteries isolated from intact rats. After 15 days of NO2 exposure, dilatation effect of low doses of vasodilators did not differ from that of intact specimens. The functional state of the adrenergic system deteriorated faster than that of the nonadrenergic noncholinergic system as reflected by the weakening of the isoproterenol relaxation effect. On prolonged NO2 exposure, pulmonary arteries responded to the impact of all vasodilators with smaller relaxation. Dose dependence of the dilatation reaction disappeared for isoproterenol, capsaicin, beclometasone, and was less expressed for nitrosorbide and acetylcholine after 60 days of exposure. In the course of COPD model generation, the functioning of almost all neurotransmitter systems of pulmonary artery wall was negatively affected. This led to a decrease in the influence of vasodilators on pulmonary artery vascular tone and could facilitate the development of pulmonary hypertension, which is typical of COPD.

EVALUATION OF THE DEPENDENCE OF AUTOANTIBODY LEVELS AND CYTOKINES FROM THE INHALATION LOAD OF PRIORITY TOXICANTS AIR ENVIRONMENT

Air pollution has a negative impact on the human body, creating the preconditions for the formation of adaptive processes or the occurrence of pathologies. Formaldehyde, particulate matter, nitrogen oxide were proved to have an effect on the respiratory and immune systems, the latter played a key role in the formation of adaptive reactions. The purpose of the study was to assess the effect of formaldehyde, nitrogen dioxide and particulate pollutants in the air environment, the maintenance of specific autoantibodies and cytokines by means of a mathematical model. The study included 659 students. In assessing individual inhalation of chemical loadings on an organism of adolescents into account data on the content of impurities in the ambient air, indoor air, information about the organization of educational process and rest pupils, anthropometric and spirometric parameters. The content of interleukin-2 and -10, interferon - alpha and - gamma, level of specific autoantibodies that characterize the state of the immune system and lungs has been studied in adolescents. The content of specific autoantibodies and cytokines depends upon hazard indexes priority pollutants are not linear and varies depending on the level of exposure of toxicants. The levels of autoantibodies to β2- glycoprotein I and the content of α-INF and γ-INF adolescents living in air pollution by formaldehyde, nitrogen dioxide, and particulate matter may depend on the level of inhaled pollutants load by 8-11%. Inhalation of nitrogen dioxide in the organism of adolescents may contribute to the variable level of autoantibodies to the of membrane antigens lung parenchyma to 22%.

Relación de los mecanismos inmunológicos del asma y la contaminación ambiental

Introducción. Se calcula que más de 300 millones de personas alrededor del mundo padecen asma y se estima que para el año 2025 esta cifra se incremente a 400 millones debido a los contaminantes criterio. Sin embargo, dadas sus limitaciones, los estudios epidemiológicos son controversiales sobre la contaminación y el desarrollo de asma.Objetivos. Describir las diferencias y similitudes de la respuesta inmunológica de pacientes asmáticos y los modelos animales de asma alérgica después de la exposición a contaminantes criterio y elementos biológicos, para así identificar los factores inmunológicos relacionados con el desarrollo de asma.Materiales y método. Se realizó una búsqueda sistemática en las bases de datos sobre asma y los diferentes contaminantes criterio.Resultados. La respuesta Th2 es activada por la inhalación de ozono, dióxido de nitrógeno, azufre y la exposición aguda a material particulado, mientras que el contacto con ciertos tipos de pólenes y glucanos y la exposición crónica de partículas incrementa la respuesta Th1, la cual inhibe a la respuesta Th2 produciendo un “efecto protector”.Conclusiones. La respuesta Th1 podría causar baja o nula asociación entre la exposición a contaminación y el desarrollo de asma en las diferentes ciudades, adicionando de esta manera otra limitación a los estudios epidemiológicos.

Biological effects of inhaled nitrogen dioxide in healthy human subjects

Several epidemiological studies indicate that inhaled nitrogen dioxide (NO2) at low concentrations have been statistically associated with adverse health effects. However, these results are not reflected by exposure studies in humans. The aim of the study was to assess the acute functional and cellular responses to different NO2 concentrations in healthy human subjects with various techniques. Twenty-five subjects were exposed for 3h to NO2 concentrations 0, 0.1, 0.5, and 1.5ppm in a randomized crossover study design during 4 consecutive weeks. In each subject, lung function, diffusion capacity and exhaled nitric oxide were measured and inflammation markers were assessed in blood, nasal secretions, induced sputum and exhaled breath condensate. From all lung function indices under consideration, only intrathoracic gas volume was borderline significantly increased after 0.5ppm (p=0.048) compared to 0.1ppm NO2. Regarding the cellular effect parameters, the macrophage concentration in induced sputum decreased with increasing NO2 concentration, although these changes were only borderline significant (p=0.05). These results do not suggest a considerable acute adverse response in human subjects after 3h of exposure to NO2 in the NO2 concentration range investigated in this study.

Acute nitrogen dioxide inhalation induces mitochondrial dysfunction in rat brain

Recent epidemiological literatures imply that NO2 is a potential risk factor of neurological disorders. Whereas, the pathogenesis of various neurological diseases has been confirmed correlate to mitochondrial dysfunction, and mitochondria play the crucial roles in energy metabolism, free radicals production and apoptosis triggering in response to neuronal injury. Therefore, to clarify the possible mechanisms for NO2-induced neurotoxicity, in the present study, we investigated the possible effects of acute NO2 inhalation (5, 10 and 20mg/m3 with 5h/day for 7 days) on energy metabolism and biogenesis in rat cortex, mainly including mitochondrial ultrastructure, mitochondrial membrane potential, cytochrome c oxidase activity, cytochrome c oxidase (CO) and ATP synthase subunits, ATP content, and transcription factors. The results showed that NO2 exposure induced mitochondrial morphological changes in rat cortex, and the alteration was coupled with the abnormality of mitochondrial energy metabolism, including decreased respiratory complexes, reduced ATP production and increased production of ROS. Also, increased ROS in turn caused mitochondrial membrane damage, energy production defect and mitochondrial biogenesis inhibition. It suggests the significantly damaged mitochondrial energy metabolism and impaired biogenesis in rat brain after NO2 exposure, and provides a new understanding of the pathophysiological mechanisms of NO2-induced neurological disorders.

Nitrogen dioxide exposure and airway responsiveness in individuals with asthma

Controlled human exposure studies evaluating the effect of inhaled nitrogen dioxide (NO2) on the inherent responsiveness of the airways to challenge by broncho-constricting agents have had mixed results. In general, existing meta-analyses show statistically significant effects of NO2 on the airway responsiveness of individuals with asthma. However, no meta-analysis has provided a comprehensive assessment of the clinical relevance of changes in airway responsiveness, the potential for methodological biases in the original papers, and the distribution of responses. This paper provides analyses showing that a statistically significant fraction (i.e. 70% of individuals with asthma exposed to NO2 at rest) experience increases in airway responsiveness following 30-min exposures to NO2 in the range of 200 to 300 ppb and following 60-min exposures to 100 ppb. The distribution of changes in airway responsiveness is log-normally distributed with a median change of 0.75 (provocative dose following NO2 divided by provocative dose following filtered air exposure) and geometric standard deviation of 1.88. About a quarter of the exposed individuals experience a clinically relevant reduction in their provocative dose due to NO2 relative to air exposure. The fraction experiencing an increase in responsiveness was statistically significant and robust to exclusion of individual studies. Results showed minimal change in airway responsiveness for individuals exposed to NO2 during exercise.

Emission of Fine Particulate Matter and Nitrogen Dioxide from Incense Burning in Shrines, Chiang Mai, Thailand

 Abstract—The inhalation of fine particles (PM2.5) and nitrogen dioxide (NO2) has been associated with health problems. Incense burning is an important indoor source of these pollutants. This research aims to measure PM2.5 and NO2 emitted from incense burning in shrines on special occasions and during normal periods to assess the indoor air quality changes. PM2.5 samples were collected on Teflon filters using a mini volume air sampler set up inside the shrines, while NO2 samples were collected by tube type passive samplers, set up both indoors and outdoors. When special events were compared with normal occasions, the mean PM2.5 concentrations obtained from 8 and 24 hrs were significantly different (p<0.05). Moreover, their concentrations were significantly higher on Chinese New Year than on other special occasions. In the case of NO2, the concentrations were not different among a variety of special occasions, but were higher than the values measured during the normal periods. Moreover, NO2 concentrations were not found to be significantly different when the indoor and the outdoor values were compared. The values of PM2.5 and NO2 concentrations at both shrines were highest during the Chinese New Year. The main reason for this was clearly the number of visitors, which was related with the amount of incense being burned. Concentrations of NO2 and PM2.5 were well correlated (r = 0.580 - 0.779) in every occasion. It can be concluded that the amount of incense being burned played a significant role in pollutant emissions and the indoor air quality.

Nitrogen dioxide inhalation induces genotoxicity in rats

Nitrogen dioxide (NO2) is a ubiquitous reactive free-radical gas, which has been associated with momentary and chronic health effects. In the present study, comet, micronucleus (MN) and DNA–protein crosslinks (DPC) assays were used to investigate the genotoxicity following in vivo inhalation exposure of rats to NO2. The results show that inhalation exposure of rats to NO2 induced DNA strand breakage and the formation of DPC in the cells from various internal organs (brain, lung, liver, spleen, kidney and heart), as well as resulted in obvious increase of MN frequency in the bone marrow cells of rats. Furthermore, above genotoxic responses showed significant linear dose-dependent manners. These results implicate that NO2 is a genotoxic agent and these observations are informative for understanding the mechanisms of adverse effects of nitrogen dioxide.

DNA-protein Crosslinks and Micronuclei Induced by Chronic Nitrogen Dioxide Inhalation in Rats

DNA-protein Crosslinks and Micronuclei Induced by Chronic Nitrogen Dioxide Inhalation in Rats

Aversion to the inhalation of nitrogen and carbon dioxide mixtures compared to high concentrations of carbon dioxide for stunning rabbits

AbstractStunning by inhalation of nitrogen (N2) and carbon dioxide (CO2) mixtures reduces aversion compared to high concentrations of CO2 in pigs and poultry. The objective of the study was to assess the aversion to 90% of CO2 (90C) and an alternative gas mixture of 80% N2 and 20% CO2 (80N20C) in commercial rabbits (Oryctolagus cuniculus). Sixty animals, divided into two groups, were used. During the first day, the rabbits of both groups were lowered in pairs into the pit with atmospheric air and their behaviour was recorded as control. During the second day, one group was exposed, again in pairs, to 90C and the other to 80N20C for 1 min. Exploratory behaviour and general activity were assessed 2 min before the exposure, during the exposure and for 2 min subsequently. During the exposure, signs of respiratory distress, loss of balance, muscle twitching and recovery of balance were also assessed. In the control sessions (atmospheric air), animals did not show respiratory distress or muscle twitching and were less active while the crate was descending than when gas treatments were applied. The percentage of animals with respiratory distress was higher in 90C (97%) than 80N20C (40%). Muscle twitching occurred earlier in 80N20C (97%; 23.9 s) than in 90C (17%; 37.4 s). A second phase of muscle twitching occurred only in 90C at 93.0 s. Mean latency of lost of balance and recovery were lower in 80N20C (24.2 and 98.6 s, respectively) than in 90C (28.2 and 110.2 s, respectively). It is concluded that rabbits showed less signs of respiratory distress to inhalation of 80N20C than 90C but more signs of aversion than when they were exposed to atmospheric air.

Mesenchymal stem cells and the stem cell niche: a new chapter

BONE MARROW-DERIVED mesenchymal stem/stromal cells (MSCs) are self-renewing multipotent cells with therapeutic effects in diverse models of tissue injury (27). In the rodent lung, MSCs reduce collagen deposition in the bleomycin model of pulmonary fibrosis (26) and reduce lung injury and improve survival following intrapulmonary delivery of endotoxin or Escherichia coli (10, 11) and following severe gram-negative peritonitis (18). In the hyperoxia model of bronchopulmonary dysplasia, exposure to high concentrations of oxygen during early postnatal life in rats and mice causes simplification of alveolar and lung capillary structure and reduced pulmonary capillary surface area, leading to pulmonary hypertension. Two groups reported simultaneously in 2009 that MSCs given by airway to rats (12) or by blood to mice (2) during prolonged hyperoxia in early postnatal life prevented arrested alveolar growth. However, engraftment of MSCs during hyperoxia and in other models has not accounted for the therapeutic effects, thus prompting a search for other mechanisms. MSCs are potent immunomodulators, suppressing several functions of lymphocytes, natural killer cells, and monocytes (1), and reduce inflammatory cell lung infiltrates and cytokines during sepsis and acute lung injury (11, 23, 25). In addition, MSCs have direct antibacterial effects (19), secrete epithelial growth factors (21), and can rescue epithelial cellular bioenergetics with mitochondrial transfer (14). MSCs and the Stem Cell Niche

Pulmonary vascular disorders in chronic obstructive pulmonary disease as a target for therapeutic intervention

Summary. A model of chronic obstructive pulmonary disease (COPD) was reproduced in rats by intermittent inhalation of nitrogen dioxide for 60 days. Pulmonary vascular disorders were assessed by perfusion scintigraphy and measuring pulmonary artery smooth muscle reactivity under exposure of vasodilators. Disorders of pulmonary capillary blood flow occurred at early stages of COPD (15 days) and extended not only to segments but to lobes at 60 day of exposure. Dilatability of pulmonary arteries reduced that led to reduction of the smooth muscle relaxation amplitude in response to vasodilators with different mechanisms of action. Starting from 30th day, rats were given angioprotectors (rosuvastatin and sulodexide) to treat vascular disorders. Rosuvastatin did not improve pulmonary microcirculation and pulmonary artery smooth muscle reactivity. Administration of sulodexide resulted in improvement of pulmonary microcirculation with recruitment of reserve areas. Dilatable component of the pulmonary arteries increased leading to enhanced smooth muscle relaxation in response to isoproterenol and especially to nitrosorbide. So, we could assume sulodexide-dependent recovery of NO-dependent mechanism of pulmonary artery smooth muscle relaxation and partial restoration of β-adrenergic vasodilatation.

Exposure to nitrogen dioxide is not associated with vascular dysfunction in man

Background: Exposure to air pollution is associated with increased cardiorespiratory morbidity and mortality. It is unclear whether these effects are mediated through combustion-derived particulate matter or gaseous components, such as nitrogen dioxide.Objectives: To investigate the effect of nitrogen dioxide exposure on vascular vasomotor and six fibrinolytic functions.Methods: Ten healthy male volunteers were exposed to nitrogen dioxide at 4 ppm or filtered air for 1 h during intermittent exercise in a randomized double-blind crossover study. Bilateral forearm blood flow and fibrinolytic markers were measured before and during unilateral intrabrachial infusion of bradykinin (100–1000 pmol/min), acetylcholine (5–20 μg/min), sodium nitroprusside (2–8 μg/min), and verapamil (10–100 μg/min) 4 h after the exposure. Lung function was determined before and after the exposure, and exhaled nitric oxide at baseline and 1 and 4 h after the exposure.Results: There were no differences in resting forearm blood flow after either exposure. There was a dose-dependent increase in forearm blood flow with all vasodilators but this was similar after either exposure for all vasodilators (p > .05 for all). Bradykinin caused a dose-dependent increase in plasma tissue-plasminogen activator, but again there was no difference between the exposures. There were no changes in lung function or exhaled nitric oxide following either exposure.Conclusion: Inhalation of nitrogen dioxide does not impair vascular vasomotor or fibrinolytic function. Nitrogen dioxide does not appear to be a major arbiter of the adverse cardiovascular effects of air pollution.

Influence of epithelial lining fluid lipids on NO(2)-induced membrane oxidation and nitration.

Within the pulmonary epithelial lining layer (ELF), antioxidants such as ascorbic acid (AH(2)) and glutathione (GSH) react with inhaled nitrogen dioxide ((*)NO(2)) to produce reactive oxygen species (ROS) that induce cellular oxidation. Because the ELF contains unsaturated fatty acids (UFA), which potentially react with (*)NO(2) and/or the antioxidant-derived ROS, we studied the influence of aqueous phase model UFA [egg phosphatidylcholine (EggPC) liposomes] on exposure-induced oxidation and nitration of membranes. Our lung surface model used gas phase (*)NO(2) exposures of immobilized red cell membranes (RCM) overlaid with defined aqueous phases. Acetyl cholinesterase (AChE) activity, TBARS, and 3-nitrotyrosine (3-NT) were used to assess protein and lipid oxidation and RCM nitration, respectively. During (*)NO(2) exposure, AH(2) and GSH induced AChE loss and TBARS, which were unchanged with buffer only. Exposures of EggPC generated extensive TBARS but not AChE loss; addition of AH(2)/GSH to EggPC resulted in smaller AChE declines and fewer TBARS. 3-NT formation occurred with or without EggPC, low concentration antioxidants, SOD, catalase, or DTPA, but was inhibitable by desferrioxamine or high antioxidant concentrations. The data suggest that reaction/diffusion limitations govern (*)NO(2) distribution, that (*)NO(2) per se directly nitrates tyrosine residues within hydrophobic regions, and that the induction of secondary oxidative processes is dependent on nonlinear relationships among (*)NO(2) flux rates, antioxidant concentrations, and diffusivity of secondary reactive species.

Effects of Vitamin E-Deficiency and/or Nitrogen Dioxide Inhalation on Allergen-Sensitized Type IV and Type I Allergy Responses of Mice.

Effect of oxidative stress induced by vitamin E-deficiency and/or nitrogen dioxide (NO2) inhalation on Type IV and Type I allergy responses of mice was investigated. Mice were fed a vitamin E-adequate diet (control: C group) or a vitamin E-deficient diet (-E group). The vitamin E content in the blood of C and -E groups was 1.58 and 0.3 μg/ml, respectively. Mice of the C and -E groups were exposed to air or air containing NO2 (5-6 ppm) (C + NO2 and -E + NO2 groups) by feeding them the corresponding diets for 1-2 week. In the sensitization with 2,4-dinitrochlorobenzene (DNCB), the degree of lymph node cell proliferation of mice of the C + NO2 group, as assessed by lymph node assay, was similar to that of mice of the C group. While the degree of cell proliferation of mice of the -E group was lower than that of mice of the C group, the degree of cell proliferation of mice of the -E + NO2 group was higher than that of mice of the C and C + NO2 groups. While the DNCB-sensitized IgE levels of mice of the C + NO2 group were similar to those of mice of the C group, the IgE levels of mice of the -E and -E + NO2 groups were higher than those of the C and C + NO2 groups. While the trimellitic anhydride (TMA)-sensitized IgE levels of mice of the -E group were similar to those of mice of the C group, the IgE levels of mice of the C + NO2 and -E + NO2 groups were much higher. These results suggest that allergen-sensitized type IV and I allergy responses of mice are enhanced by oxidative stress induced by vitamin E-deficiency and/or NO2 inhalation.