8-hydroxy-2--deoxyguanosine and Hypersensitivity

Observational studies suggest a potentially protective role of the Mediterranean diet (MD) in allergic diseases, including asthma. Large scale randomised controlled trials (RCTs) are needed to test the hypothesised allergy-prevention benefits of a MD during pregnancy. The present two-arm pilot RCT in pregnant women at high-risk of having a child who would develop allergic disease investigated maternal recruitment, retention and acceptability of an MD dietary intervention in the UK. The trial also assessed the effect of the intervention on MD adherence scores at 12 and at 24 weeks post-randomisation.. Thirty women were recruited at around 12 weeks of gestation. Retention was high (28 out of 30; 93%). The intervention was acceptable to participants. Mean (SD) adherence to the MD at baseline was 12.4 (2.9) in the intervention arm (n = 14) and 13.0 (1.9) in the control arm (n = 16), where 24 represents maximal adherence. There was a favourable short-term change in MD score: the adjusted mean difference (intervention - control) in the change in MD score from baseline to 12 weeks post-randomisation was 2.4 (95% confidence interval = 0.6-4.2, P = 0.012).. The trial provides important insights into recruitment, retention and sustaining the dietary intervention, which will be used in the design of a large RCT.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Biomarkers; Deoxyguanosine; Diet; Diet, Mediterranean; Feasibility Studies; Female; Humans; Hypersensitivity; Infant; Male; Nitrates; Nitrous Oxide; Nutrition Assessment; Pilot Projects; Pregnancy; Pregnancy Outcome; Primary Prevention; Young Adult

This study examines the relationship between toner exposure and its health effects in terms of biomarkers which are known to assess the damages to humans caused by toxic material exposure.. The subjects were 1504 male workers aged below 50 in 2003 in a Japanese toner and photocopier manufacturing company. Personal exposure measurements, pulmonary function tests, chest X-ray examinations, biomarker measurement, and a questionnaire about respiratory symptoms were conducted. We will report about biomarker measurement in this study. Cross-sectional survey studies and a longitudinal study from 2003 to 2008 were conducted.. Few significant findings were associated with the toner exposure in both the cross-sectional and the longitudinal studies. The higher toner exposure concentrations did not induce effects on increasing biomarkers.. There was no evidence of excessive inflammatory, allergic, or oxidative stress reaction in toner-handling workers as compared to non-handling workers, despite some sporadically significant findings. There are no other reports of a longitudinal epidemiological study with regard to toner exposure; this report significantly contributes to toner exposure literature. Although in the current well-controlled working environment, the toner exposure concentrations are quite low; further studies are needed to completely understand the health effects toner may have, however small they may be.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; C-Reactive Protein; Chemical Industry; Cohort Studies; Cross-Sectional Studies; Cytokines; Deoxyguanosine; Humans; Hypersensitivity; Immunoglobulin E; Inflammation; Japan; Longitudinal Studies; Male; Manufactured Materials; Occupational Exposure; Oxidative Stress; Printing

Allergic asthma is characterized by chronic airway remodeling, which is associated with the expression of extracellular matrix proteins (ECM) by TGF-β. However, to date there are no reports demonstrating that structural proteins are directly expressed in mast cells. This study aimed to investigate whether ECM proteins are expressed in mast cells activated with antigen/antibody reaction, and whether the resolution effects of irradiation or 8-oxo-dG may contribute to allergic asthma prevention. Bone marrow-derived mast cells (BMMCs) were activated with DNP-HSA/anti-DNP IgE antibody (act-BMMCs). C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) to induce allergic asthma. Mice were treated orally with 8-oxo-dG or exposed to whole body irradiation (using (137)Cs gamma ray at a dose of 0.5 Gy) for three consecutive days 24 h after OVA challenge. Expression of extracellular matrix (ECM) proteins, TGF-β signaling molecules and NF-κB/AP-1 was determined in the BMMCs, bronchoalveolar lavage (BAL) cells or lung tissues using Western blot, polymerase chain reaction (PCR) and electrophoretic mobility shift assay (EMSA), respectively. Act-BMMCs increased expression of ECM proteins, TGF-β/TGF-β receptor I, TGF-β signaling molecules and cytokines; and increased both NF-κB and AP-1 activity. In addition, the population of mast cells; expression of mast cell markers, TGF-β signaling molecules, ECM proteins/amounts; OVA-specific serum IgE level; numbers of goblet cells; airway hyperresponsiveness; cytokines/chemokines were increased in BAL cells and lung tissues of OVA-challenged mice. All of the above end points were reduced by irradiation or 8-oxo-dG in vitro and in vivo, respectively. The data suggest that mast cells induce expression of ECM proteins through TGF-β produced in inflammatory cells of OVA mice and that post treatment of irradiation or 8-oxo-dG after OVA-challenge may reduce airway remodeling through down-regulating mast cell re-activation by TGF-β/Smad signals.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Airway Remodeling; Animals; Bone Marrow Cells; Bronchoalveolar Lavage Fluid; Deoxyguanosine; Dose-Response Relationship, Radiation; Electrophoretic Mobility Shift Assay; Extracellular Matrix Proteins; Female; Hypersensitivity; Mast Cells; Mice; Mice, Inbred C57BL; Ovalbumin; Signal Transduction; Transforming Growth Factor beta

We previously reported that 8-oxo-2'-deoxyguanosine (8-oxo-dG) suppressed airway hyperresponsiveness and allergy-associated immune responses in ovalbumin-induced allergic mice by inactivating Rac. In the present study, 8-oxo-dG was investigated for its suppression of inflammation and remodeling in lung tissues induced by allergic reaction in mice. Mice were sensitized and challenged with ovalbumin without or with oral administration of 8-oxo-dG. The mice without 8-oxo-dG administration showed the following inflammatory and airway remodeling signs: infiltration of inflammatory cells into peribronchial area, hyperplasia of mucus-secreting goblet cells in bronchial walls, increase of expressions of Muc5ac and vascular cell adhesion molecule (VCAM)-1, collagen deposition and protein expression, and matrix metalloproteinase (MMP)-2/-9 expressions. We also observed an increase of various inflammation-mediating proteins, namely IL-4, IL-5, IL-8, IL-13, TNF-α and IFN-γ, and activation of STAT1 and NF-κB. Production of reactive oxygen species and nitric oxide (NO(.)) was increased as indicated by a dramatic increase in formation of nitro-tyrosine. Importantly, Rac1 and 2 were also markedly activated. However, 8-oxo-dG suppressed all these inflammatory and tissue remodeling signs as well as activation of Rac1 and 2. These results indicate that 8-oxo-dG can inhibit allergy-induced inflammation and remodeling in airway and lung tissues through Rac inactivation.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Airway Remodeling; Animals; Collagen; Cytokines; Deoxyguanosine; Enzyme Activation; Female; Gene Expression Regulation; Goblet Cells; Hyperplasia; Hypersensitivity; Immunosuppressive Agents; Inflammation; Lung; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Inbred BALB C; Mucin 5AC; NF-kappa B; rac GTP-Binding Proteins; RNA, Messenger; STAT1 Transcription Factor; Tyrosine; Vascular Cell Adhesion Molecule-1