It has been established that ingestion of a high-fat diet increases the blood levels of lipopolysaccharides (LPS) from Gram-negative bacteria in the gut. Obesity is characterised by low-grade ...systemic and adipose tissue inflammation. This is suggested to be implicated in the metabolic syndrome and obesity. In the present review, we hypothesise that LPS directly and indirectly participates in the inflammatory reaction in adipose tissue during obesity. The experimental evidence shows that LPS is involved in the transition of macrophages from the M2 to the M1 phenotype. In addition, LPS inside adipocytes may activate caspase-4/5/11. This may induce a highly inflammatory type of programmed cell death (i.e. pyroptosis), which also occurs after infection with intracellular pathogens. Lipoproteins with or without LPS are taken up by adipocytes. Large adipocytes are more metabolically active and potentially more exposed to LPS than small adipocytes are. Thus, LPS might be involved in defining the adipocyte death size and the formation of crown-like structures. The adipocyte death size is reached when the intracellular concentration of LPS initiates pyroptosis. The mechanistic details remain to be elucidated, but the observations indicate that adipocytes are stimulated to cell death by processes that involve LPS from the gut microbiota. There is a complex interplay between the composition of the diet and microbiota. This influences the amount of LPS that is translocated from the gut. In particular, the lipid content of a meal may correlate with the amount of LPS built in to chylomicrons.
Background: Air pollution is thought to exert health effects through oxidative stress, which causes damage to DNA and lipids. Objective: We determined whether levels of oxidatively damaged DNA and ...lipid peroxidation products in cells or bodily fluids from humans are useful biomarkers of biologically effective dose in studies of the health effects of exposure to particulate matter (PM) from combustion processes. Data sources: We identified publications that reported estimated associations between environmental exposure to PM and oxidative damage to DNA and lipids in PubMed and EMBASE. We also identified publications from reference lists and articles cited in the Web of Science. Data synthesis: In the meta-analysis, the standardized mean differences (95% confidence interval) between exposed and unexposed subjects for oxidized DNA and lipids were 0.53 (0.29–0.76) and 0.73 (0.18–1.28) in blood and 0.52 (0.22–0.82) and 0.49 (0.01–0.97) in urine, respectively. The standardized mean difference for oxidized lipids was 0.64 (0.07–1.21) in the airways. Restricting analyses to studies unlikely to have substantial biomarker or exposure measurement error, studies likely to have biomarker and/or exposure error, or studies likely to have both sources of error resulted in standardized mean differences of 0.55 (0.19–0.90), 0.66 (0.37–0.95), and 0.65 (0.34–0.96), respectively. Conclusions: Exposure to combustion particles is consistenly associated with oxidatively damaged DNA and lipids in humans, suggesting that it is possible to use these measurements as biomarkers of biologically effective dose.
Abstract This study investigated toxicity of nanocarriers comprised of cationic polymer and lipid components often used in gene and drug delivery, formulated as cationic micelles and liposomes. Rats ...were injected intravenously with 10, 25 or 100 mg/kg and sacrificed after 24 or 48 h, or 24 h after the last of three intravenous injections of 100 mg/kg every other day. Histological evaluation of liver, lung and spleen, clinical chemistry parameters, and hematology indicated little effect of treatment. DNA strand breaks were increased in the lung and spleen. Further, in the dose response study we found unaltered expression levels of genes in the antioxidant response ( HMOX1 ) and repair of oxidized nucleobases ( OGG1 ), whereas expression levels of cytokines ( IL6 , CXCL2 and CCL2 ) were elevated in lung, spleen or liver. The results indicate that assessment of genotoxicity and gene expression add information on toxicity of nanocarriers, which is not obtained by histology and hematology. From the Clinical Editor This study investigates the toxicity of cationic micelles and liposomes utilized as nanocarriers in gene and drug delivery, demonstrating its effects on the lungs, spleen and liver.
The toxic and inflammatory potential of 5 different types of nanoparticles were studied in a sensitive model for pulmonary effects in apolipoprotein E knockout mice (ApoE-/-). We studied the effects ...instillation or inhalation Printex 90 of carbon black (CB) and compared CB instillation in ApoE-/- and C57 mice. Three and 24 h after pulmonary exposure, inflammation was assessed by mRNA levels of cytokines in lung tissue, cell composition, genotoxicity, protein and lactate dehydrogenase activity in broncho-alveolar lavage (BAL) fluid.
Firstly, we found that intratracheal instillation of CB caused far more pulmonary toxicity in ApoE-/- mice than in C57 mice. Secondly, we showed that instillation of CB was more toxic than inhalation of a presumed similar dose with respect to inflammation in the lungs of ApoE-/- mice. Thirdly, we compared effects of instillation in ApoE-/- mice of three carbonaceous particles; CB, fullerenes C60 (C60) and single walled carbon nanotubes (SWCNT) as well as gold particles and quantum dots (QDs). Characterization of the instillation media revealed that all particles were delivered as agglomerates and aggregates. Significant increases in Il-6, Mip-2 and Mcp-1 mRNA were detected in lung tissue, 3 h and 24 h following instillation of SWCNT, CB and QDs. DNA damage in BAL cells, the fraction of neutrophils in BAL cells and protein in BAL fluid increased statistically significantly. Gold and C60 particles caused much weaker inflammatory responses.
Our data suggest that ApoE-/- model is sensitive for evaluating particle induced inflammation. Overall QDs had greatest effects followed by CB and SWCNT with C60 and gold being least inflammatory and DNA-damaging. However the gold was used at a much lower mass dose than the other particles. The strong effects of QDs were likely due to Cd release. The surface area of the instilled dose correlated well the inflammatory response for low toxicity particles.
Background: Oxidatively generated damage to DNA has been implicated in the pathogenesis of a wide variety of diseases. The
noninvasive assessment of such damage, i.e., in urine, and application to ...large-scale human studies are vital to understanding
this role and devising intervention strategies.
Methods: We have reviewed the literature to establish the status quo with regard to the methods and meaning of measuring DNA
oxidation products in urine.
Results: Most of the literature focus upon 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), and whereas a large number of these
reports concern clinical conditions, there remains ( a ) lack of consensus between methods, ( b ) possible contribution from diet and/or cell death, ( c ) no definitive DNA repair source of urinary 2′-deoxyribonucleoside lesions, and ( d ) no reference ranges for healthy or diseased individuals.
Conclusions: The origin of 8-oxodG is not identified; however, recent cell culture studies suggest that the action of Nudix
hydrolase(s) on oxidative modification of the nucleotide pool is a likely candidate for the 8-oxodG found in urine and, potentially,
of other oxidized 2′-deoxyribonucleoside lesions. Literature reports suggest that diet and cell death have minimal, if any,
influence upon urinary levels of 8-oxodG and 8-oxo-7,8-dihydroguanine, although this should be assessed on a lesion-by-lesion
basis. Broadly speaking, there is consensus between chromatographic techniques; however, ELISA approaches continue to overestimate
8-oxodG levels and is not sufficiently specific for accurate quantification. With increasing numbers of lesions being studied,
it is vital that these fundamental issues are addressed. We report the formation of the European Standards Committee on Urinary
(DNA) Lesion Analysis whose primary goal is to achieve consensus between methods and establish reference ranges in health
and disease. (Cancer Epidemiol Biomarkers Prev 2008;17(1):3–14)
Physical activity enhances uptake of air pollutants in the lung, possibly augmenting their harmful effects on chronic lung disease during exercise.
To examine whether benefits of physical activity ...with respect to the risk of asthma and chronic obstructive pulmonary disease (COPD) are moderated by exposure to high air pollution levels in an urban setting.
A total of 53,113 subjects (50-65 yr) from the Danish Diet, Cancer, and Health cohort reported physical activity at recruitment (1993-1997) and were followed until 2013 in the National Patient Register for incident hospitalizations for asthma and COPD. Levels of nitrogen dioxide (NO
) were estimated at subject residences at the time of recruitment. We used Cox regression to associate physical activities and NO
(high/medium/low) with asthma and COPD, and then introduced an interaction term between each physical activity and NO
.
A total of 1,151 subjects were hospitalized for asthma and 3,225 for COPD during 16 years. We found inverse associations of participation in sports (hazard ratio 95% confidence interval: 0.85 0.75-0.96) and cycling (0.85 0.75-0.96) with incident asthma, and of participation in sports (0.82 0.77-0.89), cycling (0.81 0.76-0.87), gardening (0.88 0.81-0.94), and walking (0.85 0.75-0.95) with incident COPD admissions. We found positive associations between NO
and incident asthma (1.23 1.04-1.47) and COPD (1.15 1.03-1.27) hospitalizations (comparing ≥21.0 μg/m
to <14.3 μg/m
). We found no interaction between associations of any physical activity and NO
on incident asthma or COPD hospitalizations.
Increased exposure to air pollution during exercise does not outweigh beneficial effects of physical activity on the risk of asthma and COPD.
It has been suggested that air pollution may increase the risk of type 2 diabetes but data on particulate matter with diameter <2.5μm (PM2.5) are inconsistent. We examined the association between ...long-term exposure to PM2.5 and diabetes incidence.
We used the Danish Nurse Cohort with 28,731 female nurses who at recruitment in 1993 or 1999 reported information on diabetes prevalence and risk factors, and obtained data on incidence of diabetes from National Diabetes Register until 2013. We estimated annual mean concentrations of PM2.5, particulate matter with diameter <10μm (PM10), nitrogen oxides (NOx) and nitrogen dioxide (NO2) at their residence since 1990 using a dispersion model and examined the association between the 5-year running mean of pollutants and diabetes incidence using a time-varying Cox regression.
Of 24,174 nurses 1137 (4.7%) developed diabetes. We detected a significant positive association between PM2.5 and diabetes incidence (hazard ratio; 95% confidence interval: 1.11; 1.02–1.22 per interquartile range of 3.1μg/m3), and weaker associations for PM10 (1.06; 0.98–1.14 per 2.8μg/m3), NO2 (1.05; 0.99–1.12 per 7.5μg/m3), and NOx (1.01; 0.98–1.05 per 10.2μg/m3) in fully adjusted models. Associations with PM2.5 persisted in two-pollutant models. Associations with PM2.5 were significantly enhanced in never smokers (1.24; 1.09–1.42), and augmented in obese (1.25; 1.06–1.47) and subjects with myocardial infarction (1.32; 0.86–2.02), but without significant interaction.
Fine particulate matter may the most relevant pollutant for diabetes development among women, and non-smokers, obese women, and heart disease patients may be most susceptible.
•Evidence on association of PM2.5 with diabetes is inconsistent.•We linked residential PM2.5 to diabetes incidence in Danish Nurse Cohort.•We found 39% (4–86%) increased risk of diabetes per 10μg/m3 increase in PM2.5.•PM2.5 may be the most relevant pollutant for diabetes development.•Non-smokers, obese, and heart disease patients may be most susceptible.
•Higher socioeconomic position is associated with mostly beneficial home environments.•However, certain sources of pollution may be higher in these homes.•Affective disorders, may be especially ...strongly related to the home environment.•Housing age, type and household composition cluster with a number of indoor factors.•Mould and moisture correlate, while candle burning is largely unrelated to other factors.
Housing and indoor home environments are associated with the risk of infections and asthma in children. To better understand the determinants and characteristics of these environments, we aimed to describe the associations between parental health and socioeconomic position and housing and indoor home environments of children in Denmark, and the clustering of the factors within these environments.
Offspring in the Danish National Birth Cohort (DNBC) whose parents responded to the 11-year follow-up were eligible for inclusion. We included complete cases only. Data on the indoor and housing environments (i.e. variables on housing, sources of gaseous and particle pollution, mould and moisture, and pets) were collected through an online questionnaire responded to by a parent. Data on socioeconomic position were obtained through linkage with registry data on maternal education at offspring birth and household equivalized income at offspring birth. Data on parental health were obtained by linking self-reported data from the 11-year follow-up for mother and father with administrative registry data for the mother. We present descriptive statistics and exploratory factor analyses.
A total of 42 723 offspring were included for analyses. The distributions of nearly all indoor and housing environments differed according to educational and income strata, with patterns similar for both education and income. Generally, higher parental educational and income strata had more favorable indoor and housing environments (less secondhand smoking, gas stove use, mould and condensation and higher house ownership, detached house dwellings and newer building age). However, candle use was approximately similar between strata, fireplace use among lower educational and income strata tended towards the extremes (none or daily), and water damage was more common among higher educational and income strata. Parental health was strongly associated with housing and indoor home environment factors - especially parental affective disorders was strongly associated with mould. Four factors were extracted from the exploratory factor analyses, relating primarily in order of extraction to: housing ownership, mould and moisture, candle use and household density.
Parental health and socioeconomic position are strongly related to housing and indoor home environments. Additionally, several factors in these environments correlate strongly and cluster together. Observational studies on associations and causal effects of factors in the indoor and housing environments of children on their morbidity, must consider both of these conclusions to arrive at valid estimates and effects.
Health impact assessment (HIA) of exposure to air pollution is commonly based on city level (fine) particle concentration and may underestimate health consequences of changing local traffic. Exposure ...to traffic-related air pollution can be assessed at a high resolution by modelling levels of nitrogen dioxide (NO2), which together with ultrafine particles mainly originate from diesel-powered vehicles in urban areas. The purpose of this study was to estimate the health benefits of reduced exposure to vehicle emissions assessed as NO2 at the residence among the citizens of Copenhagen Municipality, Denmark.
We utilized residential NO2 concentrations modelled by use of chemistry transport models to calculate contributions from emission sources to air pollution. The DYNAMO-HIA model was applied to the population of Copenhagen Municipality by using NO2 concentration estimates combined with demographic data and data from nationwide registers on incidence and prevalence of selected diseases, cause specific mortality, and total mortality of the population of Copenhagen. We used exposure-response functions linking NO2 concentration estimates at the residential address with the risk of diabetes, cardiovascular diseases, and respiratory diseases derived from a large Danish cohort study with the majority of subjects residing in Copenhagen between 1971 and 2010. Different scenarios were modelled to estimate the dynamic impact of NO2 exposure on related diseases and the potential health benefits of lowering the NO2 level in the Copenhagen Municipality.
The annual mean NO2 concentration was 19.6 μg/m3 and for 70% of the population the range of exposure was between 15 and 21 μg/m3. If NO2 exposure was reduced to the annual mean rural level of 6 μg/m3, life expectancy in 2040 would increase by one year. The greatest gain in disease-free life expectancy would be lifetime without ischemic heart disease (1.4 years), chronic obstructive pulmonary disease (1.5 years for men and 1.6 years for women), and asthma (1.3 years for men and 1.5 years for women). Lowering NO2 exposure by 20% would increase disease-free life expectancy for the different diseases by 0.3–0.5 years. Using gender specific relative risks affected the results.
Reducing the NO2 exposure by controlling traffic-related air pollution reduces the occurrence of some of the most prevalent chronic diseases and increases life expectancy. Such health benefits can be quantified by DYNAMO-HIA in a high resolution exposure modelling. This paper demonstrates how traffic planners can assess health benefits from reduced levels of traffic-related air pollution.
•Nitrogen oxide concentration can serve as a proxy of exposure to traffic-related air pollution.•The annual mean nitrogen oxide concentration is 19.6 μg/m3 in Copenhagen.•One-year gain in life expectancy by lowering nitrogen oxide exposure to rural level•Marked increase in disease-free life expectancies by reducing nitrogen oxide exposure
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