Effects of environmental contaminants in inflammatory bowel disease: a systematic review

Introduction: The Inflammatory Bowel Disease (IBD) is characterized by a chronic inflammation of the gastrointestinal tract and it has two important forms: Crohn’s Disease and Ulcerative Colitis. Although the pathophysiology of the disease is mostly unknown, an interaction between the immune system, genetics, microbiome and environmental factors seems to be responsible for the disease onset. The role of environmental factors in the pathophysiology of this disease is reinforced if we consider the rapid growth in incidence and prevalence rates of IBD in areas where the incidence was previously low as, for example, Asia. However, the literature on the role of environmental factors in IBD is reduced and is not systematized. Hence, in this work a Systematic Review of the literature was performed. Materials and methods: For this systematic review the methodology “Navigation Guide Method for Grading Human Evidence” was used [1]. The research was carried out in three databases (Scopus, Web of Science, PubMed / MEDLINE). The inclusion criteria used were: research articles with original human data, clinically diagnosed inflammatory bowel disease, quantification of environmental contaminants and study of the association between environmental contaminants and inflammatory bowel disease. Only articles written in Portuguese, English, French or Spanish were included. Results: Sixteen studies were included in this systematic review. Of these, 13 studied Inflammatory Bowel Disease in general, 2 studies included only patients with Crohn’s Disease and 1 study included only patients with Ulcerative Colitis. The most studied environmental contaminants were sulfur dioxide, nitrogen dioxide, carbon monoxide, particulate matter (PM), perfluorooctanoic acid, aluminum, iron, zinc, copper, titanium dioxide, silicates and endotoxins. We also identified different categories of studies, 4 studies on the effects of air pollution, 3 on the intake of contaminated water and 3 on the effects of diet. Additionally, 2 studies evaluated the serum concentrations of contaminants, 1 studied the impact of exposure to house dust, 2 attempted a cell characterization of IBD patients and in another colitis was induced. Overall, the quality of evidence was rated “moderate to low” and the strength of evidence as “Inadequate evidence on toxicity”. Discussion and conclusions: In this systematic review, we have identified different classes of environmental contaminants associated with IBD, but studies reporting their concentration in biological matrices are rare. Based on a moderate to low level of quality, the available evidence gathered in this Systematic Review is insufficient to access the role of environmental contaminants in inflammatory bowel disease. New epidemiological studies are necessary

A circular toxicity approach to isoprostanes: From markers of oxidative stress, to epidemiological warning systems and agents of aquatic toxicity

Isoprostanes (IsoPs) are a class of oxidation products naturally formed in vivo that are indicative of endogenous oxidative stress. In individuals with chronic and oxidative stress related diseases, IsoPs are increased to pathological levels. Since they are excreted through urine into sewage systems, IsoPs can be detected in wastewater treatment plants' (WWTPs) effluents and thus can be used to evaluate the health status of a given population. The underlying principle is that higher isoprostanes WWTPs’ levels correspond to populations undergoing higher levels of oxidative stress, and thus disease. However, IsoPs are not eliminated by WWTPs and will end up being released into the aquatic environment, where they will be available for uptake by aquatic species. Being bioactive molecules, it has been suggested that IsoPs in the environment may elicit oxidative stress in aquatic organisms. In this context, we have critically reviewed the available data on IsoPs as products and effectors of toxicity, and propose the new concept of “circular toxicity”. In general, IsoPs excreted by humans as a consequence of oxidative stress are released into the aquatic environment where they may interact with aquatic organisms and induce the production of more IsoPs. These stress markers, in turn, will also be excreted, increasing the already high levels of stressors in the aquatic environment and thus create an escalating cycle of oxidative stress

Editorial: Animal Poisoning and Biomarkers of Toxicity

The worldwide incidence of animal poisoning is unknown. Despite reports pieced together by networks of veterinary clinics and poison control centers, their coverage is usually limited due to widespread under-reporting of cases (1–3). There are several reasons for this reality, being one of the major the wide gaps of knowledge regarding toxicosis agents and their profile (particularly in terms of toxicity mechanisms), since these encompass an extensive variety of synthetic chemicals, molecules of plant and animal origin, as well as drugs (both of use and abuse) (1–3). Together with the lack of specific and sensitive analytical techniques for their detection and quantification, this reality leads to reports being usually submitted in incomplete form, and presented in a case-by case manner (4–6). This situation has created uncertainty when comparing poisoning with other types of clinical findings, such as infectious diseases, traumatic injuries or malignant neoplasms, since toxicosis would come out, at least apparently, as an uncommon cause of disease (3). This has led to appeals for more cooperation and information sharing between countries and institutions (1, 3), even inside “data-rich regions” (7), which typically include North America and Europe. The disproportionately higher volumes of available information in these areas also contribute to introduce geographic biases in available information (2). This reality is perfectly illustrated by European and North American floras, that, despite their disparity in the number of hazardous species (Europe has a much lower number), are both fairly well characterized. Contrastingly, African flora, which is at least as rich in hazardous species as the North American, has been reduced to seemingly anecdotal reports (8, 9). Even in Europe, despite the already mentioned lower number of hazardous species, the number of poisonings (affecting livestock and companion animals) attributed to wild, illicit drug or houseplants (mostly by ingestion) is considerable, since they contain chemical substances in sufficient quantities to cause toxic effects. In the particular case of companion animals, the majority of reported cases refers ingestion of ornamental plants (as opposed to wild), as the source of toxicity, particularly at certain times of the year (8). In addition to plant toxicity, available information indicates that the incidence of animal toxicosis from all causes does not seem to be declining. In the 2010's, a series of reports (10–12) detailed the prevalent toxicants affecting different groups of animals. The authors identified toxic plants and mycotoxins as the most common toxic agents involved in livestock and poultry poisoning, with additional cases being reported for metals (Cu, Pb), pesticides (endosulfan, lindane), and industrial chemicals (e.g., dioxins, polychlorinated biphenyls, dibenzofurans) (11). Regarding companion animals, frequent causes of poisoning include the exposure to anticoagulant rodenticides (coumarins), herbicides (paraquat), and insecticides (organophosphates, carbamate, strychnine, metaldehyde). Also, the inadequate use of human and veterinary pharmaceuticals, and the exposure to household products accounted for a noteworthy part of registered toxicosis reports (10). Wildlife species are frequently victims of primary (deliberate), but also of secondary poisonings (typically top predators). Metals and metalloids (Pb, Zn, As, Cu, Tl, Cd, and Hg) and pesticides (mostly anticholinergics and anticoagulants) were identified as frequent, often fatal, poisoning agents. In aquatic ecosystems, point or diffuse sources of chemicals and/or from industrial, agricultural, and urban runoff contribute to poisoning incidents. Additionally, chemicals released during environmental catastrophes (which could include any of the previous categories) are a significant cause of poisoning. The type of toxicants described more than two decades ago are, in a large number of cases, not the same, since, at least in the case of synthetic chemicals (including pharmaceuticals) many of them, were banned by legislation. However, new molecules (whose harmlessness is still to be entirely proven) were developed, manufactured in large scales, and started being used in their place. Despite this (partial) change of agents, current reports indicate the continuity of poisoning events toward animals (4, 6, 13–17). Consequently, researchers in this area face the paramount task of unraveling the underlying mechanisms (such as the toxicokinetics and toxicodynamics models and the adverse outcome pathways-AOPs) of new toxicants created by the continuous outpouring of new synthetic chemicals developed for the industry, the agrobusiness and household products market, as well as the growing sector of natural extracts. Biomarkers can act as indicators or signallers of events occurring in biological systems (18). By permitting the measurement of changes in molecules, biochemical processes, cells, tissues, organs and entire organisms (encompassing physiology, pathology, or behavior) in response to external insult, they provide nuclear knowledge in order to deliver accurate diagnosis under the form of biomarkers of exposure, effects and susceptibility, as well as enabling to delineate therapeutic interventions, and the improvement of key aspects of the drug development process (19). Additionally, they can be noninvasive and can translate between species. In fact, some authors consider that the most valuable are those that can be simultaneously used in animals and humans (19). In this Research Topic of Frontiers in Veterinary Science/Veterinary Pharmacology and Toxicology, 7 manuscripts were published: 1 Review, 5 original Research Articles and 1 Brief Research Report, whose main results and contributions are briefly presented below

Tobacco smoke as a risk factor for allergic sensitization in adults: Conclusions of a systematic review and meta-analysis

Allergic sensitization to aeroallergens is a common phenomenon and a crucial step in the development of allergic diseases. Nonetheless, the influence of tobacco smoke exposure on the development of allergic sensitization in adults is quite complex and not totally understood. Therefore, our objective was to systematically review the existing evidence regarding this topic and to perform a meta-analysis of the data collected from the included studies

Acute toxicity of plant extracts towards Daphnia magna

The demand for natural based products for the cosmetics industry is increasing sharply and therefore the search for new alternatives to the traditionally used plants is growing. These alternative plants can be an important source of bioactive compounds under a circular economy approach. Within the framework of Inovep project, several plant species, some of which autochthonous from Portugal, were identified as potential sources of bioactive compounds, namely: gum rockrose (Cistus ladanifer), curry plant (Helichrysum italicum), hop (Humulus lupulus), Mediterranean thyme (Thymbra capitata) and basil (Ocimum basilicum). Considering the potential future use of these plant extracts by the industry, it is necessary to assess the risk associated with their introduction into the ecosystem. This work aims to evaluate the toxic effects of different extracts of these five species. Acute toxicity tests using the model organism Daphnia magna were performed and the immobilization after 24 and 48 hours of exposure was evaluated. The EC50 (the concentration estimated to immobilize 50 per cent of the Daphnia) varied from 201.8±3.28 x10-5 mg.L-1 at 24 hours and 199.5±5.9410x10-5 mg.L-1 at 48 hours for Cistus ladanifer extract and 11.2±0.2403 mg.L- 1 at 24 hours and 11.2±0.4095 mg.L-1 at 48 hours for Thymbra capitata essential oil. For Humulus lupulus, Helichrysum italicum, Thymbra capitata in the form of hidrolate, and Ocimum basilicum no immobilization was observed until the highest concentrations tested for various types of extracts, suggesting these extracts present low to no risk towards D. magna

Exploring frailty-related biomarkers and potential influence of environmental factors

Recent evidence advocates that healthy ageing may be possible, with morbidity compressed to later years. One area of concern is the burden of environmentally induced disease in susceptible populations. Older adults are a well-recognized susceptible population due to the decline of immune defences and the burden of multiple chronic diseases. As a susceptible population, the burden of environmentally induced disease and lifestyle factors is an increasing concern. Frailty is an age-related syndrome expected to increase over the next decades given the observed demographic shift. This syndrome has been identified to be the most common condition leading to disability, institutionalization and death in the older adults and the risk factors associated with its development are yet to be clarified. The main aim of the present study is to investigate a relation between frailty status, biomarkers and environmental exposures

Mercury levels in biological matrices from inhabitants of Estarreja, Portugal

Humans are exposed to mercury trough several pathways including the consumption of contaminated seafood and ingestion of contaminated house dust. We have previously demonstrated that mercury levels in house dust samples from Estarreja region are amongst the highest reported in Portugal. Here we report the levels of total mercury in different biological matrices from 88 adult individuals from Estarreja (age: 37-83, median: 68). Mercury was detected in all samples analysed, with the highest levels being found in hair (range: 560-4540 ng/g, median: 1680 ng/g), followed by fingernails (range: 215-1740 ng/g, median: 844 ng/g), toenails (range: 144-1850 ng/g, median: 555 ng/g), blood (range: 0.97-18.4 ng/g, median: 6.70 ng/g) and urine (range: 0.15-5.14 ng/g, median: 0.61 ng/g). The hair to blood ratio (H:B) varied between 147 and 616, with a median value of 274, which is only 9% higher than the H:B ratio proposed by the Word Health Organization . The concentrations of mercury in hair were very strongly correlated with the concentrations in blood (p0.001). Such results suggest that a urine levels reflect the exposure to a different species of mercury, reinforcing previous studies that propose urine as a suitable matrix for inorganic mercury whereas blood, hair and nails are suitable matrices for methylmercury exposure.Ana C Sousa acknowledges the financial support from University of Aveiro, in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19 (A.C.A. Sousa)publishe

Personal care products in matched human and environmental samples collected under the framework of RESPIRA Project

The indoor environment is an important source of exposure to microbial communities that may deleteriously affect human respiratory health. Recent studies demonstrated that the microbial community structure can be altered by the use of household products such as antimicrobial agents. Hence, in order to understand the modulation of the indoor microbiome by household products and their joint effect in the respiratory status of COPD patients we evaluated the levels of antimicrobials agents in dust samples and matched urine samples from patients with COPD. Overall, the concentrations in dust samples are one to two orders of magnitude higher that the concentrations in human urine. Triclosan was detected in all the dust samples, triclocarban was detected in 82% of the dust samples and parabens in 90% to 100% of the samples. In urine samples, triclosan was detected in 56% of the samples, triclocarban was always bellow detection limit (0.25 ng/mL) and parabens detection frequency varied widely (23-84%). Interestingly, the highest level reported in dust for triclosan (1200 ng/g) corresponded to the house of the patient with the highest triclosan concentration in urine (140 ng/mL) and at that house high levels of antibiotic resistant bacteria were found. Such results suggest that the use of antimicrobials might be associated with the presence of resistant bacteria and thus deserve to be further studied.publishe

House dust fungal communities’ characterization: a double take on the six by sixty by six (6 × 60 × 6) project

Fungi are a group of microbes that are found with particular incidence in the indoor environment. Their direct toxicity or capability of generating toxic compounds has been associated with a large number of adverse health effects, such as infectious diseases and allergies. Given that in modern society people spend a large part of their time indoors; fungal communities’ characterization of this environmental compartment assumes paramount importance in the comprehension of health effects. House dustThis work was supported by European Funds through COMPETE and by National Funds through the Portuguese Science Foundation (FCT) within project PEstOE/SAU/UI0709/2014. Ana C. A. Sousa and Sónia D. Coelho acknowledge FCT for the grants SFRH/BPD/65884/2009 and SFRH/ BD/78168/2011 (supported by funding from the Human Potential Operational Programme POPH, inscribed in the National Strategic Reference Framework and partially subsidized by the European Social Fund).info:eu-repo/semantics/publishedVersio