RESUMEN
The six week eruption of Eyjafjallajökull volcano in 2010 produced heavy ash fall in a sparsely populated area of southern and south eastern Iceland and disrupted European commercial flights for at least 6 days. We adopted a protocol for the rapid analysis of volcanic ash particles, for the purpose of informing respiratory health risk assessments. Ash collected from deposits underwent a multi-laboratory physicochemical and toxicological investigation of their mineralogical parameters associated with bio-reactivity, and selected in vitro toxicology assays related to pulmonary inflammatory responses. Ash from the eruption of Grímsvötn, Iceland, in 2011 was also studied. The results were benchmarked against ash from Soufrière Hills volcano, Montserrat, which has been extensively studied since the onset of eruptive activity in 1995. For Eyjafjallajökull, the grain size distributions were variable: 2-13 vol% of the bulk samples were <4 µm, with the most explosive phases of the eruption generating abundant respirable particulate matter. In contrast, the Grímsvötn ash was almost uniformly coarse (<3.5 vol%<4 µm material). Surface area ranged from 0.3 to 7.7 m2 g(-1) for Eyjafjallajökull but was very low for Grímsvötn (<0.6 m2 g(-1)). There were few fibre-like particles (which were unrelated to asbestos) and the crystalline silica content was negligible in both eruptions, whereas Soufrière Hills ash was cristobalite-rich with a known potential to cause silicosis. All samples displayed a low ability to deplete lung antioxidant defences, showed little haemolysis and low acute cytotoxicity in human alveolar type-1 like epithelial cells (TT1). However, cell-free tests showed substantial hydroxyl radical generation in the presence of hydrogen peroxide for Grímsvötn samples, as expected for basaltic, Fe-rich ash. Cellular mediators MCP-1, IL-6, and IL-8 showed chronic pro-inflammatory responses in Eyjafjallajökull, Grímsvötn and Soufrière Hills samples, despite substantial differences in the sample mineralogy and eruptive styles. The value of the pro-inflammatory profiles in differentiating the potential respiratory health hazard of volcanic ashes remains uncertain in a protocol designed to inform public health risk assessment, and further research on their role in volcanic crises is warranted.
Asunto(s)
Contaminantes Atmosféricos/toxicidad , Pulmón/efectos de los fármacos , Erupciones Volcánicas/análisis , Línea Celular/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Humanos , Radical Hidroxilo/metabolismo , Islandia , Inflamación/inducido químicamente , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Pulmón/fisiopatología , Minerales/análisis , Tamaño de la Partícula , Medición de Riesgo , Dióxido de Silicio , Pruebas de ToxicidadRESUMEN
More than half the world's population still rely on burning biomass fuels to heat and light their homes and cook food. Household air pollution, a common component of which is inhalable particulate matter (PM), emitted from biomass burning is associated with increased vulnerability to respiratory infection and an enhanced risk of developing chronic obstructive pulmonary disease. In the light of an emerging hypothesis linking chronic PM exposure during childhood and increased vulnerability to respiratory diseases in adulthood, in a chain of events involving oxidative stress, reduced immunity and subsequent infection, the aim of this study was to characterise the oxidative potential (OP) of PM collected during the burning of wood and mixed biomass, whilst cooking food in the Kathmandu Valley, Nepal. Our assessments were based on the capacity of the particles to deplete the physiologically relevant antioxidants from a validated, synthetic respiratory tract lining fluid (RTLF). Incubation of mixed biomass and wood smoke particles suspensions with the synthetic RTLF for 4 h resulted in a mean loss of ascorbate of 64.76 ± 16.83% and 83.37 ± 14.12% at 50 µg/ml, respectively. Reduced glutathione was depleted by 49.29 ± 15.22% in mixed biomass and 65.33 ± 13.01% in wood smoke particles under the same conditions. Co-incubation with the transition metal chelator diethylenetriaminepentaacetate did not inhibit the rate of ascorbate oxidation, indicating a negligible contribution by redox-active metals in these samples. The capacity of biomass smoke particles to elicit oxidative stress certainly has the potential to contribute towards negative health impacts associated with traditional domestic fuels in the developing world.
Asunto(s)
Contaminantes Atmosféricos/análisis , Biomasa , Humo/análisis , Madera/química , Femenino , Humanos , Exposición por Inhalación/efectos adversos , Exposición por Inhalación/análisis , Oxidación-Reducción , Humo/efectos adversosRESUMEN
This study isolated the effects of maternal hypoxia independent of changes in maternal nutrition on maternal circulatory and placental molecular indices of oxidative stress and determined whether maternal antioxidant treatment conferred protection. Pregnant rats were subjected to normoxic pregnancy or 13% O2 chronic hypoxia for most of gestation with and without maternal treatment with vitamin C in the drinking water. Maternal hypoxia with and without vitamin C did not affect maternal food or water intake and led to a significant increase in maternal and fetal haematocrit. At gestational day 20, maternal plasma urate and L-cysteine concentrations, and placental levels of 4-hydroxynonenal and heat shock protein 70 were increased while placental heat shock protein 90 levels were decreased in hypoxic pregnancy. The induction of maternal circulatory and placental molecular indices of oxidative stress in hypoxic pregnancies was prevented by maternal treatment with vitamin C. Maternal hypoxia during pregnancy with or without vitamin C increased placental weight, but not total or compartmental volumes. Maternal treatment with vitamin C increased birth weight in both hypoxic and normoxic pregnancies. The data show that maternal hypoxia independent of maternal undernutrition promotes maternal and placental indices of oxidative stress, effects that can be prevented by maternal treatment with vitamin C in hypoxic pregnancy. While vitamin C may not be the ideal candidate of choice for therapy in pregnant women, and taking into consideration differences in ascorbic acid metabolism between rats and humans, the data do underlie that antioxidant treatment may provide a useful intervention to improve placental function and protect fetal growth in pregnancy complicated by fetal hypoxia.
Asunto(s)
Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Peso al Nacer/efectos de los fármacos , Hipoxia/metabolismo , Estrés Oxidativo/efectos de los fármacos , Placenta/efectos de los fármacos , Animales , Animales Recién Nacidos , Ácido Ascórbico/sangre , Catalasa/metabolismo , Cisteína/sangre , Modelos Animales de Enfermedad , Femenino , Hematócrito , Hipoxia/fisiopatología , Placenta/metabolismo , Embarazo , Complicaciones del Embarazo/metabolismo , Complicaciones del Embarazo/fisiopatología , Complicaciones del Embarazo/prevención & control , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Ácido Úrico/sangreRESUMEN
Episodes of hypoxia in utero present a potentially serious challenge to the fetus, but are counteracted by defence responses including marked redistribution of blood flow from peripheral circulations to the brain. Here, we report the novel observation that the oxidant tone is an important modulator of this cardiovascular defence. Using pregnant Welsh Mountain sheep surgically prepared for long-term recording, we investigated in vivo the effects on the fetal cardiovascular defence to acute hypoxaemia of fetal treatment with the antioxidant vitamin C. The mechanisms via which vitamin C may affect the vascular oxidant tone were investigated by monitoring fetal plasma concentrations of nitrates and nitrites, by determining changes in the activity of superoxide dismutase (SOD) in fetal plasma, and by investigating the effect of vitamin C treatment on the fetal cardiovascular defence to hypoxaemia following nitric oxide (NO) synthase blockade. Fetal treatment with vitamin C markedly depressed the normal femoral constrictor response to acute hypoxaemia in the fetus (5.2 ± 1.0 vs. 1.1 ± 0.3 mmHg (ml min(-1))(-1), mean ± s.e.m.; P < 0.05) an effect which was completely restored following NO synthase blockade (6.2 ± 1.3 mmHg (ml min(-1))(-1)). Compared to saline infusion, fetal treatment with vitamin C during acute hypoxaemia also significantly increased fetal plasma SOD activity from normoxic baseline (-8.9 ± 6.5 vs. 15.0 ± 6.6% inhibition, P < 0.05) and decreased the plasma concentration ratio of nitrate:nitrite from normoxic baseline (ΔNO3(-):NO2(-); 0.15 ± 0.30 vs. -0.29 ± 0.11, P < 0.05). The data provide in vivo evidence of redox modulation of redistribution of blood flow in the fetus, part of the fetal brain sparing during acute hypoxaemic stress.
Asunto(s)
Sistema Cardiovascular/fisiopatología , Feto/fisiología , Hipoxia/fisiopatología , Animales , Antioxidantes/uso terapéutico , Ácido Ascórbico/sangre , Ácido Ascórbico/uso terapéutico , Análisis de los Gases de la Sangre , Femenino , Hipoxia/tratamiento farmacológico , Hipoxia/metabolismo , Modelos Animales , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Nitritos/metabolismo , Oxidación-Reducción , Embarazo , Ovinos , Superóxido Dismutasa/metabolismoRESUMEN
Fluoride has been in focus as a possible causal agent for respiratory symptoms amongst aluminium potroom workers for several decades. Previously, using bronchoalveolar lavage (BAL), we demonstrated airway inflammation in healthy volunteers 24 hours after exposure to hydrogen fluoride (HF). The objective of the present study was to examine early lung responses to HF exposure. Bronchoscopy with BAL was performed 2 hours after the end of 1-hour exposure to HE Significant reductions in the total cell number and the number of neutrophils and lymphocytes were observed in bronchoalveolar portion (BAP), whereas there were no significant changes in the bronchial portion (BP). Significantly decreased concentrations of beta2-MG, IL-6 and total protein were found in both BAP and BP. Additionally, IL-8 was significantly reduced in BP, and ICAM-1 and albumin were present in lower concentrations in BAP. Lung function measurements were not affected by HF exposure. These reported effects are presumably transitory, as many were not present in the airways 24 hours after a similar HF exposure.
Asunto(s)
Contaminantes Ocupacionales del Aire/toxicidad , Líquido del Lavado Bronquioalveolar , Ácido Fluorhídrico/toxicidad , Neumonía/inmunología , Administración por Inhalación , Adulto , Antioxidantes/análisis , Biomarcadores/análisis , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Recuento de Células , Humanos , Masculino , Neumonía/inducido químicamenteRESUMEN
AIMS: To explore the effects in normal and asthmatic adults of exposure to 200 ppb sulphur dioxide (SO2) and 200 microg/m3 and 2000 microg/m3 aerosols of ammonium bisulphate (AB) and sulphuric acid (SA) (MMD 0.3 microm). METHODS: Exposures were placebo controlled, for one hour at rest, double blind in random order. DeltaFEV1 was the primary outcome; secondary outcomes included symptoms, ventilation, exhaled nitric oxide (NO) concentrations, and nasal lavage fluid ascorbic (AA) and uric acid (UA) concentrations. RESULTS: There were no significant changes in spirometry or symptoms with any exposure in either group. SO2 exposure was associated with an increased respiratory rate relative to air exposure in the asthmatic group (SO2: 958.9 breaths/hour; air: 906.8 breaths/hour) but the mean volume breathed did not differ significantly (SO2: 318.8 litres; air: 311.4 litres). AB exposures were associated with a significant rise in [NO] in the asthmatic (+1.51 ppb, and +1.39 ppb), but not in the normal group. Mean pre- and post-exposure [AA] tended to be higher in the normal than in the asthmatic group. Within each group, [AA] did not change significantly with any exposure. Post-exposure [UA] were greater than pre-exposure concentrations for all exposures, significantly so in the normal group for all exposures except SO2. There were no significant differences in the mean change in [UA] for any exposure relative to air. CONCLUSIONS: The pollutant exposure concentrations employed in this study were generally much greater than ambient. It is unlikely that short lived exposures at lower concentrations would show significant effects, but effects of longer term lower concentration exposures cannot be ruled out.
Asunto(s)
Contaminantes Atmosféricos/toxicidad , Asma/fisiopatología , Dióxido de Azufre/toxicidad , Adulto , Sulfato de Amonio/toxicidad , Antioxidantes/metabolismo , Ácido Ascórbico/metabolismo , Asma/metabolismo , Método Doble Ciego , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Masculino , Mucosa Nasal/metabolismo , Óxido Nítrico/metabolismo , Ácidos Sulfúricos/toxicidad , Ácido Úrico/metabolismoRESUMEN
The elderly are frequently classified as being particularly susceptible to air pollution. The basis of this increased sensitivity is not known but it is likely that it is linked to age-related impaired function of the lung. However, given this uncertainty and increased impact of air pollution of this section of the community there is a need to explore the mechanisms involved. Gaseous air pollutants such as ozone and nitrogen dioxide, or many of the components adsorbed onto the surface of respirable particles, are either powerful oxidants or capable of generating free radicals. If unabated, oxidants can cause injury to the delicate cells that line the respiratory tract. Small molecular weight antioxidant defences present in respiratory tract lining fluid (RTLF) represent the first line of defence against a range of oxidants that enter the lung. The quantity and quality of the RTLF airways antioxidant network are, therefore, likely to be important determinants of the impact of the oxidant challenge on the underlying respiratory epithelium. As yet, comprehensive information on the distribution and variability of respiratory tract lining fluid antioxidant defences is only available in young, mainly healthy volunteers. Studies undertaken in patients with a range of respiratory diseases suggest that marked changes in the distribution of respiratory tract lining fluid antioxidants can occur. Information is not currently available on the impact of ageing on the respiratory tract lining fluid antioxidant defence network. As several respiratory tract lining fluid antioxidants are of dietary origin, the elderly, who often have different dietary patterns to younger individuals, may have decreased availability of important antioxidants. Given these possibilities, a better understanding of respiratory tract lining fluid antioxidant defences in the aged lung is warranted.
Asunto(s)
Contaminación del Aire/efectos adversos , Enfermedades Pulmonares/fisiopatología , Pulmón/fisiopatología , Anciano , Envejecimiento/fisiología , Antioxidantes/farmacología , Humanos , Enfermedades Pulmonares/etiología , Oxidantes/efectos adversos , Sistema Respiratorio/inmunologíaRESUMEN
The development of asthmalike symptoms among aluminum potroom workers has been associated with exposure to fluorides. In the present study, the immediate nasal response in humans was examined subsequent to short-term hydrogen fluoride (HF) exposure. Ten healthy subjects were exposed to HF (3.3-3.9 mg/m(3)) for 1 h. Nasal lavage (NAL) was performed before, immediately after, and 1.5 h after the end of exposure. Control lavages were performed on the same subjects at the same time points but without HF exposure. At the end of HF exposure, 7 of 10 individuals reported upper airway symptoms. A significant increase was observed in the number of neutrophils and total cells, while there was a decrease in cell viability. The changes in neutrophil numbers correlated significantly with the reported airway symptoms. HF also induced a significant increase in tumor necrosis factor-alpha and the total protein content of NAL fluid. Among the eicosanoids, prostaglandin E(2), leukotriene B(4), and peptide leukotrienes were elevated after exposure. Of the antioxidants measured, the concentration of uric acid increased after exposure. In conclusion, exposure to HF induced immediate nasal inflammatory and antioxidant responses in healthy human volunteers. These findings may contribute to a further understanding of the way HF exerts damage to the airways and show that HF could represent an occupational hazard.
Asunto(s)
Contaminantes Ocupacionales del Aire/efectos adversos , Antioxidantes/análisis , Eicosanoides/biosíntesis , Ácido Fluorhídrico/efectos adversos , Líquido del Lavado Nasal/química , Neutrófilos/citología , Trastornos Respiratorios/inducido químicamente , Enfermedad Aguda , Administración por Inhalación , Adulto , Supervivencia Celular/efectos de los fármacos , Humanos , Recuento de Leucocitos , Masculino , Líquido del Lavado Nasal/citología , Trastornos Respiratorios/metabolismoRESUMEN
BACKGROUND: Endothelium-derived nitric oxide (NO) selectively enhances myocardial relaxation. In experimental left ventricular hypertrophy (LVH), this endothelium-dependent LV relaxant response is impaired despite a preserved response to exogenous NO. We investigated the potential role of reactive oxygen species (ROS) in this defect. METHODS AND RESULTS: Short-term treatment with the antioxidants vitamin C (10 micromol/L) or deferoxamine (500 micromol/L) restored LV relaxant responses to the NO agonists bradykinin (10 nmol/L) and substance P (100 nmol/L) in isolated ejecting hearts of aortic-banded guinea pigs. Substance P decreased the time to onset of LV relaxation (tdP/dt(min)) by -6.8+/-1.7 ms in the presence of vitamin C and by -8.9+/-2.2 ms in the presence of deferoxamine compared with -0.8+/-2.2 ms in the absence of antioxidants (P<0.05 either antioxidant versus control). A similar restoration of relaxant response to substance P was observed in the presence of the superoxide dismutase mimetic, Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (10 micromol/L), but not with tetrahydrobiopterin or L-arginine. Protein expression of the NADPH oxidase subunits gp91-phox and p67-phox and myocardial NADPH oxidase activity were significantly increased (P<0.05) in the banded group compared with shams. CONCLUSIONS: An increase in ROS, most likely derived at least in part from NADPH oxidase, is responsible for the impaired endothelial regulation of LV relaxation in LVH. These are the first data to potentially link increased NADPH oxidase-derived ROS with a defect in cardiac contractile function in a pathological setting.
Asunto(s)
Biopterinas/análogos & derivados , Endotelio Vascular/fisiopatología , Ventrículos Cardíacos/fisiopatología , Hipertrofia Ventricular Izquierda/fisiopatología , Contracción Miocárdica/fisiología , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Arginina/farmacología , Ácido Ascórbico/farmacología , Biopterinas/farmacología , Deferoxamina/farmacología , Sinergismo Farmacológico , Endotelio Vascular/efectos de los fármacos , Depuradores de Radicales Libres/farmacología , Glutatión/metabolismo , Cobayas , Ventrículos Cardíacos/efectos de los fármacos , Hipertrofia Ventricular Izquierda/metabolismo , Técnicas In Vitro , Masculino , Malondialdehído/metabolismo , Metaloporfirinas/farmacología , Contracción Miocárdica/efectos de los fármacos , NADPH Oxidasas/metabolismo , Oxidación-Reducción , Especies Reactivas de Oxígeno/metabolismo , Sustancia P/farmacologíaRESUMEN
The air pollutant ozone induces both airway inflammation and restrictions in lung function. These responses have been proposed to arise as a consequence of the oxidizing nature of ozone, depleting endogenous antioxidant defenses with ensuing tissue injury. In this study we examined the impact of an environmentally relevant ozone challenge on the antioxidant defenses present at the surface of the lung in two groups known to have profound differences in their antioxidant defense network: healthy control (HC) and mild asthmatic (MA) subjects. We hypothesized that baseline differences in antioxidant concentrations within the respiratory tract lining fluid (RTLF), as well as induced responses, would predict the magnitude of individual responsiveness. We observed a significant loss of ascorbate (ASC) from proximal (-45.1%, p <.01) and distal RTLFs (-11.7%, p <.05) in healthy subjects 6 h after the end of the ozone challenge. This was associated (Rs, -0.71, p <.01) with increased glutathione disulphide (GSSG) in these compartments (p =.01 and p <.05). Corresponding responses were not seen in asthmatics, where basal ASC concentrations were significantly lower (p <.01) and associated with elevated concentrations of GSSG (p <.05). In neither group was any evidence of lipid oxidation seen following ozone. Despite differences in antioxidant levels and response, the magnitude of ozone-induced neutrophilia (+20.6%, p <.01 [HC] vs. +15.2%, p =.01 [MA]) and decrements in FEV(1) (-8.0%, p <.01 [HC] vs. -3.2%, p <.05 [MA]) did not differ between the two groups. These data demonstrate significant differences between the interaction of ozone with RTLF antioxidants in MA and HC subjects. These responses and variations in basal antioxidant defense were not, however, useful predictive markers of group or individual responsiveness to ozone.
Asunto(s)
Antioxidantes/metabolismo , Asma/metabolismo , Disulfuro de Glutatión/agonistas , Pulmón/metabolismo , Neutrófilos/metabolismo , Ozono , Adulto , Ácido Ascórbico/antagonistas & inhibidores , Ácido Ascórbico/metabolismo , Asma/inducido químicamente , Asma/diagnóstico , Pruebas de Provocación Bronquial , Broncoscopía , Método Doble Ciego , Femenino , Disulfuro de Glutatión/metabolismo , Humanos , Pulmón/citología , Pulmón/efectos de los fármacos , Masculino , Persona de Mediana Edad , Neutrófilos/efectos de los fármacos , Ozono/efectos adversos , Valor Predictivo de las Pruebas , Pruebas de Función Respiratoria , Sistema Respiratorio/citología , Sistema Respiratorio/efectos de los fármacos , Sistema Respiratorio/metabolismoRESUMEN
Chronic lung disease of prematurity (CLD) remains a common cause of morbidity and mortality in preterm infants. Oxygen toxicity remains a major risk factor for the development of CLD and as a consequence the antioxidant status of CLD babies is a major focus of interest. In the present study, we determined whether ascorbate, urate, and total glutathione concentrations were decreased in infants who developed CLD when compared to those who did not. From 34 preterm infants, 141 serial bronchoalveolar lavage fluid (BALF) and plasma samples were collected: 12 developed CLD (median gestation 26 weeks, range 23-28 weeks, median birth weight 780 g, range 630-1070 g), 16 developed and recovered from respiratory distress syndrome (RDS) (median gestation 31 weeks, range 26-39 weeks, median birth weight 1820 g, range 840-4160 g), and six were ventilated for non-respiratory reasons, (median gestation 35 weeks, range 32-38 weeks, median birth weight 2180 g, range 1100-2860 g). Following birth, the concentration of BALF ascorbate, urate and glutathione decreased over the 1st week in all three groups. Thereafter, BALF ascorbate increased in RDS and control infants during the 2nd week but this increase was delayed by 2 weeks in the CLD infants. No differences were noted between the RDS and CLD groups for urate and total glutathione in BALF or urate in plasma. BALF protein concentration was similar in all three groups except for a rise at day 7 in the CLD group but this did not reach statistical significance. Conclusion. A delayed increase in bronchoalveolar lavage fluid ascorbate concentration might be associated with an increased risk of developing chronic lung disease of prematurity.
Asunto(s)
Antioxidantes/metabolismo , Ácido Ascórbico/metabolismo , Displasia Broncopulmonar/metabolismo , Recien Nacido Prematuro , Análisis de Varianza , Líquido del Lavado Bronquioalveolar/química , Estudios de Casos y Controles , Femenino , Glutatión/metabolismo , Humanos , Recién Nacido , Masculino , Ácido Úrico/metabolismoRESUMEN
The aim of this study was to investigate the cellular and biochemical events associated with repeated exposures to ozone. Twenty-three healthy subjects underwent single exposures to 200 ppb ozone and to filtered air (FA), as well as repeated exposures to 200 ppb ozone on 4 consecutive days, each for 4 h of intermittent exercise. Bronchoalveolar lavage was performed and mucosal biopsies were taken 20 h after the single or the last of the repeated exposures. As compared with FA, the single exposure to ozone caused a decrease in FEV(1), an increase in the percentages of neutrophils and lymphocytes, the concentrations of total protein, IL-6, IL-8, reduced glutathione, urate, and ortho-tyrosine in BAL fluid (BALF), but no changes in the cellular composition of biopsy. After the repeated exposure, the effect on lung function was abolished and differential cell counts in BALF were not significantly different from those after FA. However, the concentrations of total protein, IL-6, IL-8, reduced glutathione, and ortho-tyrosine were still increased. IL-10 could only be detected in BALF after repeated ozone exposures. Furthermore, macroscopic scores for bronchitis, erythema, and hypervulnerability of airway mucosa were increased, as well as numbers of neutrophils in bronchial mucosal biopsies. Our data demonstrate that airway inflammation persists after repeated ozone exposure, despite attenuation of some inflammatory markers in BALF and adaptation of lung function.
Asunto(s)
Hiperreactividad Bronquial/inducido químicamente , Líquido del Lavado Bronquioalveolar/inmunología , Mediadores de Inflamación/metabolismo , Ozono/toxicidad , Adulto , Bronquios/efectos de los fármacos , Bronquios/inmunología , Bronquios/patología , Hiperreactividad Bronquial/inmunología , Hiperreactividad Bronquial/patología , Pruebas de Provocación Bronquial , Relación Dosis-Respuesta a Droga , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Recuento de Leucocitos , Masculino , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Neutrófilos/patología , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/patologíaRESUMEN
Many cystic fibrosis (CF) patients have increased circulating levels of oxidation products and/or decreased antioxidant status. This study investigated whether treatment of pulmonary exacerbations decreased oxidative stress in CF patients. Seventeen adult patients were studied at the beginning and end of treatment with intravenous antibiotics. Plasma concentrations of the antioxidants ascorbic acid, alpha-tocopherol, uric acid and total reduced thiols, together with plasma retinol, lipid hydroperoxides, malondialdehyde and protein carbonyl levels were determined. Median (interquartile range) pretreatment and post-treatment levels were compared using the Wilcoxon signed rank test. Clinical resolution was reflected by improved spirometry. Significant increases were observed in plasma ascorbic acid (pre 30.4 (15.7-38.6) microM, post 35.2 (27.3-49.6) microM), alpha-tocopherol (pre 19.7 (13.6-25.2) microM, post 25.2 (19.3-31.6) microM) and retinol (pre 1.9 (1.5-2.5) microM, post 2.7 (1.7-3.5) microM). No change in plasma total reduced thiols occurred following treatment (pre 409 (366-420) microM, post 392 (366-423) microM), whereas uric acid fell with treatment (pre 307 (274-394) microM, post 260 (216-317) microM). Neither plasma protein carbonyls or malondialdehyde levels altered with treatment (protein carbonyls pre 0.47 (0.28-1.27), post 0.67 (0.42-0.83) nM x mg protein(-1); malondialdehyde pre 0.75 (0.53-1.18), post 0.84 (0.65-1.15) microM). Lipid hydroperoxides levels did decrease following treatment (53 (18-85) versus 17 (10-55) nM). This study demonstrated that treatment of infective exacerbations resulted in increased plasma levels of some antioxidant vitamins. No immediate change in plasma protein oxidation was observed, but lipid oxidation was decreased.
Asunto(s)
Antibacterianos/administración & dosificación , Antioxidantes/metabolismo , Infecciones Bacterianas/sangre , Infecciones Bacterianas/tratamiento farmacológico , Fibrosis Quística/sangre , Fibrosis Quística/tratamiento farmacológico , Vitamina E/sangre , Adulto , Antioxidantes/análisis , Ácido Ascórbico/sangre , Infecciones Bacterianas/microbiología , Biomarcadores/sangre , Fibrosis Quística/microbiología , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Pronóstico , Recurrencia , Esputo/microbiología , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
Lung lining fluid antioxidants represent a potentially important protective barrier of lung epithelial cells to damaging effects of air pollutants, yet no information is apparently available concerning lung lining fluid antioxidants in broilers. Therefore, goals of this study were to establish uric acid, ascorbic acid, reduced (GSH) and oxidized (GSSG) glutathione, and protein concentrations in lung lining fluid obtained from male broiler chickens maintained for 6 to 7 wk within environmentally controlled rooms (Control) or chronically exposed to high levels of dust and ammonia within a broiler rearing house (House). The entire respiratory tract was carefully removed following an overdose of anesthetic and lavage fluid was collected after flushing the lungs with heparin-saline (10 mL per lung). There was no difference in GSH, but GSSG, uric acid, and protein concentrations were higher in House birds than in Controls. An increase in the GSSG to total glutathione (GSx) ratio, an indicator of oxidative stress, was also observed in birds maintained in the House environment. Ascorbic acid was not detected in House-reared birds and detected in only 4 of 12 Controls. Regression analysis revealed positive correlations between lung lining fluid protein and uric acid (r = 0.71; P < 0.01), protein and GSSG (r = 0.73; P < 0.01), and uric acid and GSSG concentrations (r = 0.69, P < 0.01). Additionally, GSSG was positively correlated (r = 0.66; P < 0.01) with the right ventricular weight ratio, an index commonly used in identifying the development of pulmonary hypertension syndrome in broilers. These data, the first to document lung lining fluid antioxidants in avian species, indicate an oxidative stress can be detected in fluid of broilers exposed to high levels of dust and ammonia in a simulated poultry house environment.
Asunto(s)
Antioxidantes/análisis , Líquido del Lavado Bronquioalveolar/química , Pollos/fisiología , Estrés Oxidativo/fisiología , Ventilación/normas , Animales , Ácido Ascórbico/análisis , Estudios de Cohortes , Dieta/veterinaria , Glutatión/análisis , Glutatión/química , Disulfuro de Glutatión/análisis , Vivienda para Animales/normas , Masculino , Oxidación-Reducción , Proteínas/análisis , Ácido Úrico/análisis , Ventilación/métodosRESUMEN
The CHO320 cell line, engineered to produce human interferon gamma was investigated with regard to its susceptibility to oxidative stress. Batch cultures of the cells grown in a bench-top bioreactor exhibited no marked response to changes in oxygen concentration between 6% and 14% whereas cell growth and recombinant protein production were inhibited by increasing the oxygen to 20%. High concentrations of hydrogen peroxide (in excess of 200 microM) were required to inhibit growth of the CHO320 cells whereas concentrations of 50 microns and 100 microM had no effect on recombinant protein production. Buthionine sulphoximine (50 microM and 100 microM) completely depleted the cells of glutathione within 24 h; however, no quantitative effect on recombinant protein production was seen. It is concluded that the CHO320 cells are, possibly as a consequence of the long selection process they have undergone, very resistant to oxidative stress.
Asunto(s)
Interferón gamma/biosíntesis , Estrés Oxidativo , Animales , Butionina Sulfoximina/farmacología , Células CHO , Cricetinae , Glutatión/metabolismo , Humanos , Peróxido de Hidrógeno/farmacología , Proteínas RecombinantesRESUMEN
Vitamin A (retinol reacts extremely rapidly (k = 1.4 x 10(9) M-1 s-1) with thiyl free radicals derived from glutathione to form a free radical with a very strong visible absorption (lambda max. = 380 nm, E max. = 4.0 x 10(4) M-1 cm-1). Arachidonate, linolenate, linoleate and ascorbate also react readily but much more slowly (k = 2.2 x 10(7), 1.9 x 10(7), 1.3 x 10(7) and 3.6 x 10(8) M-1 s-1 respectively). These results support the possibility that vitamin A might play a role in protecting lipid membranes against thiyl free radical mediated damage.
Asunto(s)
Ácido Ascórbico , Ácidos Grasos Insaturados , Glutatión , Vitamina A , Ácido Araquidónico , Ácidos Araquidónicos , Radicales Libres , Cinética , Ácido Linoleico , Ácidos Linoleicos , Ácidos Linolénicos , Relación Estructura-Actividad , Ácido alfa-LinolénicoRESUMEN
In neutral solutions, desferrioxamine (Desferal) can react with the superoxide free radical, O2.- (possibly through its protonated form HO2.), to form a relatively stable nitroxide free radical, which can have a half-life of approx. 10 min at room temperature. The formation of the radical can be largely prevented by the presence of superoxide dismutase. The radical reacts rapidly with cysteine, methionine, glutathione, vitamin C and a water-soluble derivative of vitamin E. It also reacts rapidly with alcohol dehydrogenase, causing a loss of enzyme activity. The implications of these findings for mechanistic free-radical biochemistry and iron-chelation therapy could be considerable.
Asunto(s)
Deferoxamina/farmacología , Óxidos de Nitrógeno/metabolismo , Superóxidos/metabolismo , Alcohol Deshidrogenasa/antagonistas & inhibidores , Antioxidantes/farmacología , Espectroscopía de Resonancia por Spin del Electrón , Radicales LibresRESUMEN
The reactions of organic free radicals, acting as either reductants or oxidants, have been studied by pulse radiolysis in neutral aqueous solution at room temperature. Manyhydroxyl-substituted aliphatic carbon-centred radicals and one-electron adducts have been shown to be good one-electron reductants, while several oxygen-, sulphur- and nitrogen- (but not carbon-) centred free radicals have been shown to be good one-electron oxidants. Several carbon-centred radicals can be reduced rapidly by hydrogen transfer, from undissociated thiol compounds which can thus act as catalysts facilitating the overall reduction of a carbon-centred radical by an electron-donating molecule. Kinetic considerations influenced by the one-electron redox potentials of the radical-molecule couples involved, determine whether a particular reaction predominates. In this paper examples of such reactions, involving a water-soluble derivative of vitamin E (Trolox C) and the coenzyme NADH, are described, together with studies showing (a) that even in complex multi-solute systems some organic peroxy radicals can inactiviate alcohol dehydrogenase under conditions where the superoxide radical does not, and (b) the superoxide radical can be damaging if urate is also present, and this damage can be reduced by the presence of superoxide dismutase.