Oxidative Stress In Lung Tissue Research Articles

Effect of Apocynin on Acute Lung Injury in Rats Given Interleukin-1α Intratracheally

Background: Based on the assertion that apocynin diminishes acute lung injury (ALI) by inhibition of NADPH oxidase, the effect of apocynin was tested in interleukin-1α (IL-1)-induced ALI in rats. Methods: IL-1 was insufflated into the trachea of Sprague-Dawley rats to induce ALI, and apocynin (8 mg/kg) was given intravenously for inhibition of NADPH oxidase. In addition, we determined whether apocynin inhibited generation of superoxide anions from isolated human neutrophils. Five hours after IL-1 instillation, lung injury parameters, expression of cytosolic phospholipase A2 (cPLA2) by cells from bronchoalveolar lavage (BAL), an index of oxidative stress in lung tissues (γ-glutamyltranspeptidase, activity), and ultrastructure of alveolar type II (AT II) cells were evaluated. Results: Apocynin decreased the generation of free radicals from phorbol myristate (PMA)-activated neutrophils in vitro, but did not ameliorate ALI. IL-1 induced enhancement of the expression of cPLA2 on neutrophils was not altered by apocynin. Conclusion: Apocynin induced suppression of the generation of superoxide anions from neutrophils by inhibition of NADPH oxidase does not attenuate IL-1-induced ALI in rats.

32 Hyperoxic Resuscitation Gives Increased Oxidative Stress in Lung Tissue and Influence the Capacity to Repair Base Lesions on Dna

Background/aims: Newborn resuscitation with pure oxygen may induce short- and long term pathological changes via oxidative stress. Oxygen can adversely affect all tissues of the body. We studied DNA repair activities in lung-, liver- and brain tissue 9 hours(h) after preceding hypoxia and reoxygenation. In lung tissue antioxidant capacity and DNA repair activity was assessed at both 1 and 9 h. Methods: Hypoxemia was induced by ventilation of 8% O2 in N2 and maintained until Base Excess reached -20mmol/L or mean arterial blood pressure decreased below 15mmHg. The piglets, n=5-10 in each group, were resuscitated for 15 or 30 min by ventilation with 21 or 100% O2 and observed for 1 or 9 h before lung-, liver and brain tissue samples were removed and snap-frozen. Controls went through surgery, stabilization and ventilation, but were not exposed to hypoxia and reoxygenation. Results: One hour after end of resuscitation the total antioxidant capacity in lung tissue was significant lower in the group resuscitated with 100% O2 compared to 21% (p< 0.02), but after 9h there were no difference. The DNA repair activity was significantly reduced 1h after resuscitation; in the 100% group 55% reduction vs controls(p=0.008) and 28% vs room air(p=0.047). After 9h there was still a tendency to reduced base lesion repair on DNA in tissue from the lung and prefrontal cortex. Conclusions: Hypoxia and subsequent resuscitation with 100% O2 causes increased oxidative stress and risk of cell damage and long term consequences such as accumulation of mutations in the genome.

Dual Role of Vitamin C Utilization in NO2-Induced Oxidative Stress in Lung Tissues of Mice

Earlier studies with in vitro models have revealed that application of vitamin C can act as a primary NO(2) absorption substrate to contribute to NO(2)-induced cellular injury. In the present study, we showed that the pharmacological application of vitamin C had dual role in lungs of mice exposed to NO(2), with an exacerbated oxidative stress occurring at low concentrations, as indicated by excessive reactive oxygen species production and lipid peroxidation. However, at high concentrations, vitamin C functioned as an antioxidant removing reactive oxygen species and maintaining a reducing status in cells, alleviating NO(2)-induced oxidative toxicity.

Hypoxic Stress Exacerbates Hyperoxia-Induced Lung Injury in a Neonatal Mouse Model of Bronchopulmonary Dysplasia

Background: Premature infants with lung injury often experience intermittent episodes of hypoxemia. Objective: This study investigates whether intermittent hypoxemia exacerbates oxidative stress and lung injury in neonatal mice in a hyperoxia-induced model of bronchopulmonary dysplasia (BPD). Methods: For the BPD model, 3-day-old C57Bl/6J mice were exposed to hyperoxia (65% O₂) for 4 weeks (O₂ group) or to hyperoxia and intermittent (10 min daily) hypoxia (O₂ + H group). Upon completion of O₂ or O₂ + H exposure, the degree of pulmonary alveolarization and granulocytic infiltration were examined. The severity of oxidative injury in lungs was defined by tissue glutathione and protein carbonyl content. Data were compared to those in naïve mice and mice subjected only to intermittent hypoxia. Results: Hyperoxia-exposed mice exhibited a dramatic (p < 0.0001) decrease of alveolarization, significantly increased granulocytic infiltration (p < 0.0001) and increased protein carbonyl content (p = 0.04) compared to naïve mice. However, O₂ + H mice demonstrated significantly (p = 0.03) fewer alveoli compared to their O₂ counterparts. This was associated with a significantly (p = 0.02) decreased pulmonary total/oxidized glutathione ratio and a significant (p = 0.03) elevation of protein carbonyl content. Conclusions: Thus, intermittent hypoxic stress during hyperoxic induction of BPD in mice potentiates oxidative stress in lung tissue and exacerbates alveolar developmental arrest.

Association between haplotypes of manganese superoxide dismutase (SOD2), smoking, and lung cancer risk

Tobacco smoke contains high concentrations of reactive oxygen species (ROS) that can damage DNA, proteins, and lipids. Manganese superoxide dismutase (SOD2) catalyzes the dismutation of superoxide radicals into hydrogen peroxide and protects against oxidative stress in lung tissues. Three tagSNPs were identified in one block of high linkage disequilibrium that spans the entire SOD2 gene and 5-kb promoter region. These tagSNPs, representing four haplotypes (TAA, TCA, TCG, CCG), were genotyped in 372 lung cancer cases and 605 controls. There was no association between the haplotype frequencies and the overall lung cancer risk. The TCG haplotype (6% in controls) was significantly associated with a lower risk of lung cancer in light smokers (< median pack-years; P value = 0.02) but not in heavy smokers. In histologic-specific analysis, the TCG haplotype was significantly associated with a reduced risk of lung adenocarcinoma (odds ratio = 0.39, 95% CI 0.17–0.88), but an inverse association with squamous cell carcinoma was not significant. The association with adenocarcinoma was most apparent in light smokers (haplotype-specific P value = 0.005); none of the 61 case subjects with adenocarcinoma had the TCG allele. This study suggests that subjects with the SOD2 TCG haplotype may be at decreased risk for lung adenocarcinoma and that this association may depend on smoking amount.

Short exposure to particulate matter from vehicle traffic promotes oxidative stress in lung of rats

In vitro and in vivo studies have demonstrated chronic and acute toxicity of particulate matter (PM). However, in majority these studies have been performed using high doses of PM. The aim of this study was to verify whether ambient level of PM promotes oxidative stress, and inflammatory responses in lung of rat. Adults, male, Wistar rats were exposed to ambient particles (polluted) or filtered air (control) for periods of 6 or 20 hours in Porto Alegre city, Brazil. Exposure chambers were made of glass and one (control) received a Teflon filter in the inlet (PM<10μm), whereas the other received atmospheric air (polluted). After the exposure animals were euthanized to collect lung for oxidative stress (OE) evaluation and edema. Another set of animals followed the same protocol and submitted to bronchoalveolar lavage (BAL) 24h later to determine inflammatory parameters. Rats breathing polluted air for 20h showed increase of OE in lung tissue ([MDA] nmol/mg protein: polluted=0.226±0.02 X control=0.148±0.01 - p = 0.040) and increase of total cells (X105) in BAL (polluted=2.61±0.51 X control= 5.01±0.81- p=0.041). There was not difference in theses outcomes in the group of rats breathing pollution for 6 h (total cells – polluted= 3.86±0.42 X control=3.02±0.37 p=0.464; OE ([MDA] nmol/mg protein: polluted=0.145±0.01 X control=0.142±0.01- p=0.950). The OE imposed by 20h exposure to polluted air was not associated with significant increases in the lung water content (p>0.05). This study shows that short-term inhalation of low concentrations of PM in “real world” exposure promotes biological hazards. Supported by: FFFCMPA, CAPES, CNPq.

Changes in antioxidant status of lung tissue in experimental diabetes in rabbits

Objectives: Hyperglycaemia can result in oxidative stress which may affected as cellular tissue damage. Design and methods: After 3, 6, 12 and 24 weeks of hyperglycaemia oxidative stress related parameters were measured in lung tissue of diabetic and control rabbits. Results: Decreased activities of antioxidative compounds and intensification of lipid peroxidation process were found in diabetic lung. Conclusions: The data obtained suggest that hyperglycaemia induces oxidative stress in lung tissue which may play an important role in pathogenesis of diabetic complications.

Cigarette smoking induces an increase in oxidative DNA damage, 8-hydroxydeoxyguanosine, in a central site of the human lung.

To evaluate the effect of cigarette smoking on oxidative stress in lung tissues, we compared the levels of a type of oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OH-dG), in tissue obtained from the central sites of lungs from 14 current smokers, seven ex-smokers and nine non-smokers. The mean level of 8-OH-dG in the lung tissues from smokers was 1.43-fold higher than that of the non-smokers (the difference was statistically significant, P = 0.0262). A positive correlation between the 8-OH-dG levels in normal lung tissues and the Brinkman index was obtained from smokers and ex-smokers (r = 0.525; P = 0.0134). A positive correlation was also obtained for the 8-OH-dG levels in normal lung tissues and the number of cigarettes smoked per day (r = 0.436; P = 0.0132). These results suggest that oxidative DNA damage is induced in lung DNA by cigarette smoking.

A novel lung slice system with compromised antioxidant defenses.

In order to facilitate the study of oxidative stress in lung tissue, rat lung slices with impaired antioxidant defenses were prepared and used. Incubation of lung slices with the antineoplastic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (100 microM) in an amino acid-rich medium for 45 min produced a near-maximal (approximately 85%), irreversible inhibition of glutathione reductase, accompanied by only a modest (approximately 15%) decrease in pulmonary nonprotein sulfhydryls (NPSH) and no alteration in intracellular ATP, NADP+, and NADPH levels. The amounts of NADP(H), ATP, and NPSH were stable over a 4-hr incubation period following the removal from BCNU. The viability of the system was further evaluated by measuring the rate of evolution of 14CO2 from D-[14C(U)]-glucose. The rates of evolution were almost identical in the compromised system when compared with control slices over a 4-hr time period. By using slices with compromised oxidative defenses, preliminary results have been obtained with paraquat, nitrofurantoin, and 2,3-dimethoxy-1,4-naphthoquinone.

A Novel Lung Slice System with Compromised Antioxidant Defenses

In order to facilitate the study of oxidative stress in lung tissue, rat lung slices with impaired antioxidant defenses were prepared and used. Incubation of lung slices with the antineoplastic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (100 microM) in an amino acid-rich medium for 45 min produced a near-maximal (approximately 85%), irreversible inhibition of glutathione reductase, accompanied by only a modest (approximately 15%) decrease in pulmonary nonprotein sulfhydryls (NPSH) and no alteration in intracellular ATP, NADP+, and NADPH levels. The amounts of NADP(H), ATP, and NPSH were stable over a 4-hr incubation period following the removal from BCNU. The viability of the system was further evaluated by measuring the rate of evolution of 14CO2 from D-[14C(U)]-glucose. The rates of evolution were almost identical in the compromised system when compared with control slices over a 4-hr time period. By using slices with compromised oxidative defenses, preliminary results have been obtained with paraquat, nitrofurantoin, and 2,3-dimethoxy-1,4-naphthoquinone.

Vitamin E and selenium regulate balance between β-adrenergic and muscarinic responses in rat lungs

The effects of hydrogen peroxide on the β-adrenergic and muscarinic responses of the rat trachea muscle were studied in vitro, after feeding rats, for 6 weeks, either a diet deficient in vitamin E and selenium or a control diet. In the control situation after incubation with 1 mM hydrogen peroxide for 30 min, a reduction of the maximal response to methacholine of 39% occurred whereas no p D 2 shift could be demonstrated. Moreover, no response to isoprenaline after precontraction with 3 × 10 −7 M methacholine was left. In the deficient situation, we found a reduction to 64% of the response to methacholine after incubation with 1 mM hydrogen peroxide. Again isoprenaline became inactive, i.e. no relaxation with isoprenaline was observed after precontraction with 3 × 10 −7 M methacholine. We therefore conclude that vitamin E and selenium protect against oxidative stress in lung tissue and thus regulate the (patho-) physiological balance between adrenergic and muscarinic responses.