Overproduction of reactive oxygen and nitrogen species can result from exposure to environmental pollutants, such as ionising and nonionising radiation, ultraviolet radiation, elevated concentrations of ozone, nitrogen oxides, sulphur dioxide, cigarette smoke, asbestos, particulate matter, pesticides, dioxins and furans, polycyclic aromatic hydrocarbons, and many other compounds present in the environment. It appears that increased oxidative/nitrosative stress is often neglected mechanism by which environmental pollutants affect human health. Oxidation of and oxidative damage to cellular components and biomolecules have been suggested to be involved in the aetiology of several chronic diseases, including cancer, cardiovascular disease, cataracts, age-related macular degeneration, and aging. Several studies have demonstrated that the human body can alleviate oxidative stress using exogenous antioxidants. However, not all dietary antioxidant supplements display protective effects, for example, β-carotene for lung cancer prevention in smokers or tocopherols for photooxidative stress. In this review, we explore the increases in oxidative stress caused by exposure to environmental pollutants and the protective effects of antioxidants.

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The Protective Role of Antioxidants in the Defence against ROS/RNS-Mediated Environmental Pollution

A common feature of environmental irritants is their ability to cause local inflammation which could alter airway function. The principal targets of such injury are the epithelial cells lining the airway passages and the lower respiratory gas-exchange areas. While host atopy is a recognized risk factor for airway inflammation, atopy alone cannot cause asthma. We hypothesize that susceptibility to persistent airway inflammation in atopic individuals is characterized by an inherited deficiency in the effectiveness of detoxification of inhaled irritants and products of oxidative stress such as reactive oxygen species (ROS). Our case-control studies show that polymorphisms at the glutathione S-transferase, GSTP1, locus on chromosome 11q13 may account for variation in host response to oxidative stress, a key component of airway inflammation. Frequency of the GSTP1 Val/Val genotype is reduced in atopic subjects compared with nonatopic subjects. Trend analysis also shows a significant decrease of GSTP1 Val/Val (with parallel increase of GSTP1 Ile/Ile) genotype frequency with increasing severity of airflow obstruction/bronchial hyperresponsiveness. The implication of specific polymorphisms at the GSTP1 locus in airway inflammation is entirely novel: however, GST are recognized as a supergene family of enzymes critical in 1) cell protection from the toxic products of ROS-mediated reactions, 2) modulation of eicosanoid synthesis.

Polymorphisms at the glutathione S-transferase, GSTP1 locus: a novel mechanism for susceptibility and development of atopic airway inflammation.

The combination of environmental chamber exposure and bronchoalveolar lavage (BAL) was used to study the effects of the common air pollutant nitrogen dioxide (NO2). Eighteen healthy nonsmokers were exposed to NO2 during 20 min in an exposure chamber during light bicycle ergometer work. All subjects were examined with BAL at least 3 wks before exposure, as a reference. The subjects were re-examined with BAL, in groups of eight, 24 h after exposure to 4, 7 and 10 mg NO2.m.3 (2.25, 4.0 and 5.5 ppm), respectively. An inflammatory cell response was found after exposure to all concentrations. An increase in the number of lymphocytes in BAL fluid was observed after 7 and 10 mg.m.3 (p less than 0.05 and 0.02, respectively). An increase in the number of mast cells, that appears to be dose-dependent, was found after exposure to all concentrations. The proportion of lysozyme positive alveolar macrophages was elevated after exposure to 7 mg.m.3. The inflammatory mediators fibronectin, hyaluronan, angiotensin converting enzyme (ACE) and beta 2-microglobulin were unchanged by exposure. Due to the findings of inflammatory cell changes far below the peak exposure limits for work places in industrialized countries, 9-18 mg.m.3, the safety of these limits is questioned. Studies are in progress in our laboratory using BAL to evaluate the effects of repeated NO2 exposure.

https://erj.ersjournals.com/content/erj/4/3/332.full.pdf

Inflammatory cell response in bronchoalveolar lavage fluid after nitrogen dioxide exposure of healthy subjects: a dose-response study

Following the basal descriptive studies of the bronchoalveolar inflammatory cell response induced by single exposure with nitrogen dioxide (NO2) in man, it was considered important to clarify the cell response to repeated exposure with NO2. This investigation was, therefore, undertaken with bronchoalveolar lavage (BAL) 3 weeks before and 24 h after six repeated exposures with 4 ppm NO2 (7 mg.m-3) in ten healthy volunteers. The exposures were performed during 20 min and every second day. Analysis of the recovered BAL fluid demonstrated that repeated exposures to NO2 caused a lung cell response different from that reported after a single exposure. Amounts of lavaged alveolar macrophages, B-cells, and natural killer (NK)-cells were decreased and the T-helper-inducer/cytotoxic-suppressor cell ratio was altered, but there was no lymphocytosis or mastocytosis as after single exposure. Lymphocyte numbers in peripheral blood were reduced after exposure. These results suggest that repeated exposure with NO2 adversely affects the immune defence. This could contribute to the increased susceptibility to airway infections reported to be associated with NO2 exposure.

https://erj.ersjournals.com/content/erj/5/9/1092.full.pdf

Effects of repeated exposure to 4 ppm nitrogen dioxide on bronchoalveolar lymphocyte subsets and macrophages in healthy men.

Pregnant women exposed to extensive environmental contamination by oxidized nitrogen compounds were studied at parturition, their neonatal health status was assessed and the involvement of oxidative stress in pathology was evaluated. Methemoglobin in maternal and cord blood was measured as a biomarker of individual exposure. Blood lipid peroxides and glutathione (reduced and total) were determined as oxidative stress biomarkers. Birthweight, Apgar scores, and clinical diagnosis at birth were used as neonatal health endpoints. Elevated exposure to oxidized nitrogen compounds was associated with increased lipid peroxidation in both maternal and cord blood. Poor birth outcome was associated with high blood lipid peroxides. Controlling for maternal age, parity, and smoking did not affect the relationships materially. The results showed that maternal/fetal exposure to oxidized nitrogen compounds is associated with increased risk of adverse birth outcome and suggest a role of oxidative damage in the pathogenic pathway.

Exposure to Oxidized Nitrogen: Lipid Peroxidation and Neonatal Health Risk

The toxicity of ozone and nitrogen dioxide is generally ascribed to their oxidative potential. In this study their toxic mechanism of action was compared using an intact cell model. Rat alveolar macrophages were exposed by means of gas diffusion through a Teflon film. In this in vitro system, ozone appeared to be 10 times more toxic than nitrogen dioxide. α‐Tocopherol protected equally well against ozone and nitrogen dioxide. It was demonstrated that α‐tocopherolprovided its protection by its action as a radical scavenger and not by its stabilizing structural membrane effect, as (1) concentrations of a‐tocopherol that already provided optimal protection against ozone and nitrogen dioxide did not influence the membrane fluidity of alveolar macrophages and (2) neither one of the structural α‐tocopherol analogs tested (phytol and the methyl ether of a‐tocopherol) could provide a protection against ozone or nitrogen dioxide comparable to the one provided by a‐tocopherol. It was concluded that reactive interme...

R.A. Hempenius

Papers

Toxicity of ozone and nitrogen dioxide to alveolar macrophages: comparative study revealing differences in their mechanism of toxic action.

Comparative study on the toxicity of methyl linoleate-9,10-ozonide and cumene hydroperoxide to alveolar macrophages.

Toxicity of methyl linoleate ozonide in the rat.

Ozone-induced lung toxicity: mediated by ozonides.

Molecular orbital study on the glutathione-dependent detoxication of ozonides.