8-hydroxy-2--deoxyguanosine and Respiration-Disorders

Air pollution is a leading risk factor for global mortality and morbidity. Oxidative stress is a key mechanism underlying air-pollution-mediated health effects, especially in the pathogenesis/exacerbation of airway impairments. However, evidence lacks on subgroups at higher risk of developing more severe outcomes in response to air pollution. This multi-centre study aims to evaluate the association between air pollution and oxidative stress in healthy adults and in patients affected by airway diseases from the Italian GEIRD (Gene Environment Interactions in Respiratory Diseases) multi-case control study. Overall, 1841 adults (49 % females, 20-83 years) were included from four Italian centres: Pavia, Sassari, Turin, and Verona. Following a 2-stage screening process, we identified 1273 cases of asthma, chronic bronchitis, rhinitis, or COPD and 568 controls. Systemic oxidative stress was quantified by urinary 8-isoprostane and 8-OH-dG. Individual residential exposures to NO

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Air Pollutants; Air Pollution; Case-Control Studies; Environmental Exposure; Female; Gene-Environment Interaction; Humans; Male; Nitrogen Dioxide; Oxidative Stress; Particulate Matter; Respiration Disorders; Respiratory Tract Diseases

In this study we aimed at identifying main demographic, laboratory and environmental factors influencing the level of urinary biomarkers (DNA-derived 8-oxodG and lipid membrane-derived 8-isoprostane), and deriving their adjusted 95% reference intervals (RI) in a sample of healthy people from the general population. Data from 281 healthy subjects from the Gene Environment Interactions in Respiratory Diseases survey were used in this study. Generalized additive models for location, scale and shape (GAMLSS) were used to find determinants of the biomarkers among gender, age, season and distance from collection (DFC), and to predict their RI. The RI of the biomarkers stratified by season and adjusted for DFC showed a slight statistically significant decrease in the biomarkers at the increasing DFC in two seasons, except the 8-oxodG during the warm season: median levels at the min and max values of DFC were (ng/mgcreat) 7.0-1.1 in the cold and 3.9-3.9 in the warm seasons for 8-oxodG, 0.7-0.2 in the cold and 1.3-0.6 in the warm seasons for 8-isoprostane. Both the biomarkers should be evaluated in association with the DFC and season in large epidemiological studies. The (semi)parametric GAMLSS method is a useful and flexible technique, which makes it possible to estimate adjusted RI.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers; Deoxyguanosine; Dinoprost; Female; Humans; Logistic Models; Male; Middle Aged; Models, Theoretical; Oxidative Stress; Reference Values; Respiration Disorders; Seasons; Young Adult

Oxidative stress plays an important role in aging and various diseases such as cancer, cardiovascular diseases, diabetes mellitus and bronchial asthma. However, little is known about a potential role of oxidative stress in the pathogenesis of severe motor and intellectual disabilities (SMID) in terms of respiratory disturbance, which is the most common complication. In the present study, we examined the urinary levels of oxidative stress markers, 8-hydroxy-2'-deoxyguanosine (8-OHdG), hexanoyl-lysine adduct (HEL) and acrolein-lysine adduct (ACR) in patients with SMID. The mean level of urinary 8-OHdG in SMID patients was significantly higher than that in normal controls (18.8 +/- 9.0 ng/mg Cre and 10.5 +/- 2.9 ng/mg Cre, respectively) (p < 0.01). There was no significant difference of the mean level of urinary HEL between patients with SMID and normal controls (81.9 +/- 40.3 pmol/mg Cre and 69.2 + /-37.7 pmol/mg Cre, respectively), while the mean level of ACR in patients with SMID was higher than that of normal controls (220.5 +/- 118.6 nmol/mg Cre and 144.9 +/- 62.0 nmol/mg Cre, respectively) (p < 0.05). In addition, the level of 8-OHdG was strongly correlated with the severity of respiratory disturbance evaluated as the respiratory disturbance score (RDS) (Spearman r = 0.73, n = 14, p < 0.01). In contrast, there was no correlation between the levels of these oxidative stress markers and age or medication of antiepileptic drugs. These results suggest that urinary 8-OHdG is a potentially useful biomarker for evaluating the severity of respiratory failure in patients with SMID.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acrolein; Adolescent; Adult; Biomarkers; Child; Deoxyguanosine; Female; Hexanols; Humans; Lipid Peroxidation; Male; Mental Disorders; Middle Aged; Motor Neuron Disease; Oxidative Stress; Respiration Disorders; Statistics, Nonparametric

Accumulation of high levels of mutagenic oxidative mitochondrial DNA (mtDNA) lesions like 8-oxodeoxyguanine (8-oxodG) is thought to be involved in the development of mitochondrial dysfunction in aging and in disorders associated with aging. Mice null for oxoguanine DNA glycosylase (OGG1) are deficient in 8-oxodG removal and accumulate 8-oxodG in mtDNA to levels 20-fold higher than in wild-type mice (N.C. Souza-Pinto et al., 2001, Cancer Res. 61, 5378-5381). We have used these animals to investigate the effects on mitochondrial function of accumulating this particular oxidative base modification. Despite the presence of high levels of 8-oxodG, mitochondria isolated from livers and hearts of Ogg1-/- mice were functionally normal. No differences were detected in maximal (chemically uncoupled) respiration rates, ADP phosphorylating respiration rates, or nonphosphorylating rates with glutamate/malate or with succinate/rotenone. Similarly, maximal activities of respiratory complexes I and IV from liver and heart were not different between wild-type and Ogg1-/- mice. In addition, there was no indication of increased oxidative stress in mitochondria from Ogg1-/- mice, as measured by mitochondrial protein carbonyl content. We conclude, therefore, that highly elevated levels of 8-oxodG in mtDNA do not cause mitochondrial respiratory dysfunction in mice.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aging; Animals; Deoxyguanosine; DNA Glycosylases; DNA, Mitochondrial; Free Radicals; Glutamic Acid; Humans; Liver; Malates; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mitochondria; Mitochondria, Heart; Mitochondria, Liver; Myocardium; Oxidative Stress; Oxygen; Oxygen Consumption; Rats; Respiration Disorders; Time Factors