Abstract
The incidence of metabolic disorders like type 2 diabetes and obesity continues to increase. In addition to the well-known contributors to these disorders, such as food intake and sedentary ...lifestyle, recent research in the exposure science discipline provides evidence that exposure to endocrine-disrupting chemicals like bisphenol A and phthalates via multiple routes (e.g., food, drink, skin contact) also contribute to the increased risk of metabolic disorders. Endocrine-disrupting chemicals (EDCs) can disrupt any aspect of hormone action. It is becoming increasingly clear that EDCs not only affect endocrine function but also adversely affect immune system function. In this review, we focus on human, animal, and in vitro studies that demonstrate EDC exposure induces dysfunction of the immune system, which, in turn, has detrimental effects on metabolic health. These findings highlight how the immune system is emerging as a novel player by which EDCs may mediate their effects on metabolic health. We also discuss studies highlighting mechanisms by which EDCs affect the immune system. Finally, we consider that a better understanding of the immunomodulatory roles of EDCs will provide clues to enhance metabolic function and contribute toward the long-term goal of reducing the burden of environmentally induced diabetes and obesity.
In this review, we focus on studies that demonstrate endocrine-disruptor exposure induces dysfunction of the immune system, which, in turn, has detrimental effects on metabolic health.
Chronic diseases and illnesses associated with non-specific symptoms are on the rise. In addition to chronic stress in social and work environments, physical and chemical exposures at home, at work, ...and during leisure activities are causal or contributing environmental stressors that deserve attention by the general practitioner as well as by all other members of the health care community. It seems necessary now to take "new exposures" like electromagnetic fields (EMF) into account. Physicians are increasingly confronted with health problems from unidentified causes. Studies, empirical observations, and patient reports clearly indicate interactions between EMF exposure and health problems. Individual susceptibility and environmental factors are frequently neglected. New wireless technologies and applications have been introduced without any certainty about their health effects, raising new challenges for medicine and society. For instance, the issue of so-called non-thermal effects and potential long-term effects of low-dose exposure were scarcely investigated prior to the introduction of these technologies. Common electromagnetic field or EMF sources: Radio-frequency radiation (RF) (3 MHz to 300 GHz) is emitted from radio and TV broadcast antennas, Wi-Fi access points, routers, and clients (e.g. smartphones, tablets), cordless and mobile phones including their base stations, and Bluetooth devices. Extremely low frequency electric (ELF EF) and magnetic fields (ELF MF) (3 Hz to 3 kHz) are emitted from electrical wiring, lamps, and appliances. Very low frequency electric (VLF EF) and magnetic fields (VLF MF) (3 kHz to 3 MHz) are emitted, due to harmonic voltage and current distortions, from electrical wiring, lamps (e.g. compact fluorescent lamps), and electronic devices. On the one hand, there is strong evidence that long-term exposure to certain EMFs is a risk factor for diseases such as certain cancers, Alzheimer's disease, and male infertility. On the other hand, the emerging electromagnetic hypersensitivity (EHS) is more and more recognized by health authorities, disability administrators and case workers, politicians, as well as courts of law. We recommend treating EHS clinically as part of the group of chronic multisystem illnesses (CMI), but still recognizing that the underlying cause remains the environment. In the beginning, EHS symptoms occur only occasionally, but over time they may increase in frequency and severity. Common EHS symptoms include headaches, concentration difficulties, sleep problems, depression, a lack of energy, fatigue, and flu-like symptoms. A comprehensive medical history, which should include all symptoms and their occurrences in spatial and temporal terms and in the context of EMF exposures, is the key to making the diagnosis. The EMF exposure is usually assessed by EMF measurements at home and at work. Certain types of EMF exposure can be assessed by asking about common EMF sources. It is very important to take the individual susceptibility into account. The primary method of treatment should mainly focus on the prevention or reduction of EMF exposure, that is, reducing or eliminating all sources of high EMF exposure at home and at the workplace. The reduction of EMF exposure should also be extended to public spaces such as schools, hospitals, public transport, and libraries to enable persons with EHS an unhindered use (accessibility measure). If a detrimental EMF exposure is reduced sufficiently, the body has a chance to recover and EHS symptoms will be reduced or even disappear. Many examples have shown that such measures can prove effective. To increase the effectiveness of the treatment, the broad range of other environmental factors that contribute to the total body burden should also be addressed. Anything that supports homeostasis will increase a person's resilience against disease and thus against the adverse effects of EMF exposure. There is increasing evidence that EMF exposure has a major impact on the oxidative and nitrosative regulation capacity in affected individuals. This concept also may explain why the level of susceptibility to EMF can change and why the range of symptoms reported in the context of EMF exposures is so large. Based on our current understanding, a treatment approach that minimizes the adverse effects of peroxynitrite - as has been increasingly used in the treatment of multisystem illnesses - works best. This EMF Guideline gives an overview of the current knowledge regarding EMF-related health risks and provides recommendations for the diagnosis, treatment and accessibility measures of EHS to improve and restore individual health outcomes as well as for the development of strategies for prevention.
Improved biomass cookstoves may help reduce the substantial global burden of morbidity and mortality due to household air pollution (HAP) that disproportionately affects women and children in low and ...middle income countries (LMICs).
Systematic review and meta-analysis of (quasi-)experimental studies identified from 13 electronic databases (last update: 6 April 2018), reference and citation searches and via expert consultation.
LMICs PARTICIPANTS: Women and children INTERVENTIONS: Improved biomass cookstoves MAIN OUTCOME MEASURES: Low birth weight (LBW), preterm birth, perinatal mortality, paediatric acute respiratory infections (ARIs) and COPD among women.
We identified 53 eligible studies, including 24 that met prespecified design criteria. Improved cookstoves had no demonstrable impact on paediatric lower ARIs (three studies; 11 560 children; incidence rate ratio (IRR)=1.02 (95% CI 0.84 to 1.24)), severe pneumonia (two studies; 11 061 children; IRR=0.88 (95% CI 0.39 to 2.01)), LBW (one study; 174 babies; OR=0.74 (95% CI 0.33 to 1.66)) or miscarriages, stillbirths and infant mortality (one study; 1176 babies; risk ratio (RR) change=15% (95% CI -13 to 43)). No (quasi-)experimental studies assessed preterm birth or COPD. In observational studies, improved cookstoves were associated with a significant reduction in COPD among women: two studies, 9757 participants; RR=0.74 (95% CI 0.61 to 0.90). Reductions in cough (four studies, 1779 participants; RR=0.72 (95% CI 0.60 to 0.87)), phlegm (four studies, 1779 participants; RR=0.65 (95% CI 0.52 to 0.80)), wheezing/breathing difficulty (four studies; 1779 participants; RR=0.41 (95% CI 0.29 to 0.59)) and conjunctivitis (three studies, 892 participants; RR=0.58 (95% CI 0.43 to 0.78)) were observed among women.
Improved cookstoves provide respiratory and ocular symptom reduction and may reduce COPD risk among women, but had no demonstrable child health impact.
PROSPERO: CRD42016033075.
Epigenetic mechanisms integrate both genetic variability and environmental exposures. However, comprehensive epigenome-wide analysis has not been performed across major childhood allergic phenotypes. ...We examined the association of epigenome-wide DNA methylation in mid-childhood peripheral blood (Illumina HumanMethyl450K) with mid-childhood atopic sensitization, environmental/inhalant and food allergen sensitization in 739 children in two birth cohorts (Project Viva-Boston, and the Generation R Study-Rotterdam). We performed covariate-adjusted epigenome-wide association meta-analysis and employed pathway and regional analyses of results. Seven-hundred and five methylation sites (505 genes) were significantly cross-sectionally associated with mid-childhood atopic sensitization, 1411 (905 genes) for environmental and 45 (36 genes) for food allergen sensitization (FDR<0.05). We observed differential methylation across multiple genes for all three phenotypes, including genes implicated previously in innate immunity (DICER1), eosinophilic esophagitis and sinusitis (SIGLEC8), the atopic march (AP5B1) and asthma (EPX, IL4, IL5RA, PRG2, SIGLEC8, CLU). In addition, most of the associated methylation marks for all three phenotypes occur in putative transcription factor binding motifs. Pathway analysis identified multiple methylation sites associated with atopic sensitization and environmental allergen sensitization located in/near genes involved in asthma, mTOR signaling, and inositol phosphate metabolism. We identified multiple differentially methylated regions associated with atopic sensitization (8 regions) and environmental allergen sensitization (26 regions). A number of nominally significant methylation sites in the cord blood analysis were epigenome-wide significant in the mid-childhood analysis, and we observed significant methylation - time interactions among a subset of sites examined. Our findings provide insights into epigenetic regulatory pathways as markers of childhood allergic sensitization.
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a growing epidemic worldwide, particularly in countries that consume a Western diet, and can lead to life-threatening conditions such as cirrhosis ...and hepatocellular carcinoma. With increasing prevalence of NAFLD in both children and adults, an understanding of the factors that promote NAFLD development and progression is crucial. Environmental agents, including endocrine-disrupting chemicals (EDCs), which have been linked to other diseases, may play a role in NAFLD development. Increasing evidence supports a developmental origin of liver disease, and early-life exposure to EDCs could represent one risk factor for the development of NAFLD later in life. Rodent studies provide the strongest evidence for this link, but further studies are needed to define whether there is a causal link between early-life EDC exposure and NAFLD development in humans. Elucidating the molecular mechanisms underlying development of NAFLD in the context of developmental EDC exposures may identify biomarkers for people at risk, as well as potential intervention and/or therapeutic opportunities for the disease.
The references cited in this mini-review were selected from manuscripts found through a PubMed search, without a publication year cutoff. References found in these publications provided additional articles to search and cite.
Changes in the intracellular thiol-disulfide balance are considered major determinants in the redox status/signaling of the cell. Cellular signaling is very sensitive to both exogenous and ...intracellular redox status and respond to many exogenous pro-oxidative or oxidative stresses. Redox status has dual effects on upstream signaling systems and downstream transcription factors. Redox signaling pathways use reactive oxygen species (ROS) to transfer signals from different sources to the nucleus to regulate such functions as growth, differentiation, proliferation, and apoptosis. Mitogen-activated protein kinases are activated by numerous cellular stresses and ligand-receptor bindings. An imbalance in the oxidant/antioxidant system, either resulting from excessive ROS/reactive nitrogen species production and/or antioxidant system impairment, leads to oxidative stress. Glutathione (GSH) is known to play a critical role in the cellular defense against unregulated oxidative stress in mammalian cells and involvement of large molecular antioxidants include classical antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). Cadmium (Cd), a potent toxic heavy metal, is a widespread environmental contaminant. It is known to cause renal dysfunction, hepatic toxicity, genotoxicity, and apoptotic effects depending on the dose, route, and duration of exposure. This review examines the signaling pathways and mechanisms of activation of transcription factors by Cd-induced oxidative stress thus representing an important basis for understanding the mechanisms of Cd effect on the cells.
•Heavy-metal pollution re-shaped the composition of the GI microbiota of B. raddei..•Heavy-metal pollution reduced the proportion of probiotics in the GI microbiota of B. raddei.•Heavy-metal ...pollution decreased the species diversity in the GI tract of B. raddei.
Gastrointestinal (GI) microbiota plays a very important role in maintaining its host’s health. However, the effects of environmental contamination on the GI microbiota homeostasis of amphibians have not yet been reported. The present study reveals the long-term effect of natural heavy-metal pollution on the GI microbial community diversity and structural changes of Bufo raddei (B. raddei). Basing on the 16S rRNA sequencing method, the GI microbiota of B. raddei from a heavily heavy-metal-polluted area (Baiyin, (BY)) and a relatively unpolluted area (Liujiaxia, (LJX)) were profiled. The results showed that heavy-metal pollution had caused significant shifts in the composition of the GI microbiota both at the phylum and genus levels. Specifically, Bacteroidetes dominated in the GI tract of B. raddei from BY, while Tenericutes was much more common in those from LJX. The ratio of Firmicutes/Bacteroidetes and the proportion of probiotics in the GI microbiota of B. raddei from BY were reduced compared to those from LJX, as well. Heavy-metal pollution also induced in a reduction of species diversity and decreased proportion of unique operational taxonomic units in the GI tract. In short, our results demonstrate that long-term heavy-metal exposure re-shaped the composition and decreased the species diversity of GI microbiota of B. raddei; our results also represent a novel approach to uncover the toxic effects of pollution on amphibians.
The primary goal of this study was to understand how changes in temperature and oxygen could influence social behaviour and aerobic metabolism of the Amazonian dwarf cichlid Apistogramma agassizii. ...Social hierarchies were established over a period of 96h by observing the social interactions, feeding behaviour and shelter use in groups of four males. In the experimental environment, temperature was increased to 29°C in the high-temperature treatment, and oxygen lowered to 1.0mg·L−1O2 in the hypoxia treatment. Fish were maintained at this condition for 96h. The control was maintained at 26°C and 6.6mg·L−1O2. After the experimental exposure, metabolism was measured as routine metabolic rate (RMR) and electron transport system (ETS) activity. There was a reduction in hierarchy stability at high-temperature. Aggression changed after environmental changes. Dominant and subdominant fish at high temperatures increased their biting, compared with control-dominant. In contrast, hypoxia-dominant fish decreased their aggressive acts compared with all other fish. Shelter use decreased in control and hypoxic dominant fish. Dominant fish from undisturbed environments eat more than their subordinates. There was a decrease of RMR in fish exposed to the hypoxic environment when compared with control or high-temperature fish, independent of social position. Control-dominant fish had higher RMR than their subordinates. ETS activity increased in fish exposed to high temperatures; however, there was no effect on social rank. Our study reinforces the importance of environmental changes for the maintenance of hierarchies and their characteristics and highlights that most of the changes occur in the dominant position.
Exhaled breath has joined blood and urine as a valuable resource for sampling and analyzing biomarkers in human media for assessing exposure, uptake metabolism, and elimination of toxic chemicals. ...This article focuses current use of exhaled gas, aerosols, and vapor in human breath, the methods for collection, and ultimately the use of the resulting data. Some advantages of breath are the noninvasive and self-administered nature of collection, the essentially inexhaustible supply, and that breath sampling does not produce potentially infectious waste such as needles, wipes, bandages, and glassware. In contrast to blood and urine, breath samples can be collected on demand in rapid succession and so allow toxicokinetic observations of uptake and elimination in any time frame. Furthermore, new technologies now allow capturing condensed breath vapor directly, or just the aerosol fraction alone, to gain access to inorganic species, lung pH, proteins and protein fragments, cellular DNA, and whole microorganisms from the pulmonary microbiome. Future applications are discussed, especially the use of isotopically labeled probes, non-targeted (discovery) analysis, cellular level toxicity testing, and ultimately assessing “crowd breath” of groups of people and the relation to dose of airborne and other environmental chemicals at the population level.
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