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Neurotoxicology Sep 2022Investigation of the toxicity triggered by chemicals on the human brain has traditionally relied on approaches using rodent in vivo models and in vitro cell models... (Review)
Review
Investigation of the toxicity triggered by chemicals on the human brain has traditionally relied on approaches using rodent in vivo models and in vitro cell models including primary neuronal cultures and cell lines from rodents. The issues of species differences between humans and rodents, the animal ethical concerns and the time and cost required for neurotoxicity studies on in vivo animal models, do limit the use of animal-based models in neurotoxicology. In this context, human cell models appear relevant in elucidating cellular and molecular impacts of neurotoxicants and facilitating prioritization of in vivo testing. The SH-SY5Y human neuroblastoma cell line (ATCC® CRL-2266™) is one of the most used cell lines in neurosciences, either undifferentiated or differentiated into neuron-like cells. This review presents the characteristics of the SH-SY5Y cell line and proposes the results of a systematic review of literature on the use of this in vitro cell model for neurotoxicity research by focusing on organic environmental pollutants including pesticides, 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), flame retardants, PFASs, parabens, bisphenols, phthalates, and PAHs. Organic environmental pollutants are widely present in the environment and increasingly known to cause clinical neurotoxic effects during fetal & child development and adulthood. Their effects on cultured SH-SY5Y cells include autophagy, cell death (apoptosis, pyroptosis, necroptosis, or necrosis), increased oxidative stress, mitochondrial dysfunction, disruption of neurotransmitter homeostasis, and alteration of neuritic length. Finally, the inherent advantages and limitations of the SH-SY5Y cell model are discussed in the context of chemical testing.
Topics: Adult; Animals; Cell Line, Tumor; Cell Survival; Child; Environmental Pollutants; Flame Retardants; Fluorocarbons; Humans; Neuroblastoma; Neurotoxicity Syndromes; Parabens; Pesticides; Polychlorinated Dibenzodioxins
PubMed: 35914637
DOI: 10.1016/j.neuro.2022.07.008 -
Food Research International (Ottawa,... Nov 2020Meat consumption has been increasing since the 1960s, but especially from the 1980s decade to today. Although meat means an important source of nutrients, it is also... (Review)
Review
Meat consumption has been increasing since the 1960s, but especially from the 1980s decade to today. Although meat means an important source of nutrients, it is also evident that a great consumption of this source of proteins has also a negative environmental impact. Livestock production does not only have a negative influence on GHG emissions, but also on the water footprint, water pollution, and water scarcity. With respect to human health, in 2015 the International Agency for Research on Cancer (IARC) stated that red meat was a probable carcinogen to humans (Group 2A), while consumption of processed meat was carcinogenic to humans (Group 1). Most environmental contaminants (PCDD/Fs, PCBs, PBDEs, PCNs, etc.) that are frequently found in meats are highly soluble in fats. Therefore, avoiding ingesting fats from red meats and meat products, doubtless would help in the prevention, not only of the well-known cardiovascular diseases derived of fats consumption, but also of certain kinds of cancers, mainly colorectal cancer. On the other hand, consumption of meat - especially wild meat - is related to virus infections, as many viruses have been found in wild meat trade markets. Based on the scientific literature here reviewed, we have noted that the results of the investigations conducted after the statement of the IARC, have corroborated the recommendation of reducing significantly the consumption of red meats and meat products. In turn, the reduction of meat consumption should contribute to the reduction of GHG emissions and their considerable impact on global warming and climate change. It seems evident that human dietary habits regarding meat consumption in general, and red meats and wild meats in particular, should be significantly modified downward, as much and as soon as possible.
Topics: Dibenzofurans; Humans; Meat; Meat Products; Polychlorinated Dibenzodioxins; Red Meat
PubMed: 33233049
DOI: 10.1016/j.foodres.2020.109341 -
Journal of Neurochemistry Sep 2021Acetylcholinesterase (AChE, EC 3.1.1.7) plays important roles in cholinergic neurotransmission and has been widely recognized as a biomarker for monitoring pollution by... (Review)
Review
Acetylcholinesterase (AChE, EC 3.1.1.7) plays important roles in cholinergic neurotransmission and has been widely recognized as a biomarker for monitoring pollution by organophosphate (OP) and carbamate pesticides. Dioxin is an emerging environmental AChE disruptor and is a typical persistent organic pollutant with multiple toxic effects on the nervous system. Growing evidence has shown that there is a significant link between dioxin exposure and neurodegenerative diseases and neurodevelopmental disorders, most of which involve AChE and cholinergic dysfunctions. Therefore, an in-depth understanding of the effects of dioxin on AChE and the related mechanisms of action might help to shed light on the molecular bases of dioxin impacts on the nervous system. In the past decade, the effects of dioxins on AChE have been revealed in cultured cells of different origins and in rodent animal models. Unlike OP and carbamate pesticides, dioxin-induced AChE disturbance is not due to direct inhibition of enzymatic activity; instead, dioxin causes alterations of AChE expression in certain models. As a widely accepted mechanism for most dioxin effects, the aryl hydrocarbon receptor (AhR)-dependent pathway has become a research focus in studies on the mechanism of action of dioxin-induced AChE dysregulation. In this mini-review, the effects of dioxin on AChE and the diverse roles of the AhR pathway in AChE regulation are summarized. Additionally, the involvement of AhR in AChE regulation during different neurodevelopmental processes is discussed. These AhR-related findings might also provide new insight into AChE regulation triggered by diverse xenobiotics capable of interacting with AhR.
Topics: Acetylcholinesterase; Animals; Brain; Cells, Cultured; Dioxins; Humans; Neurodegenerative Diseases; Neurons; Receptors, Aryl Hydrocarbon
PubMed: 33278027
DOI: 10.1111/jnc.15261 -
American Journal of Respiratory and... Sep 2022
Topics: Agent Orange; Humans; Idiopathic Pulmonary Fibrosis; Respiratory System; Veterans
PubMed: 35675559
DOI: 10.1164/rccm.202206-1064ED -
International Journal of Molecular... Jan 2021Poisoning by high concentrations of dioxin and its related compounds manifests variable toxic symptoms such as general malaise, chloracne, hyperpigmentation, sputum and... (Review)
Review
Poisoning by high concentrations of dioxin and its related compounds manifests variable toxic symptoms such as general malaise, chloracne, hyperpigmentation, sputum and cough, paresthesia or numbness of the extremities, hypertriglyceridemia, perinatal abnormalities, and elevated risks of cancer-related mortality. Such health hazards are observed in patients with Yusho (oil disease in Japanese) who had consumed rice bran oil highly contaminated with 2,3,4,7,8-pentachlorodibenzofuran, polychlorinated biphenyls, and polychlorinated quaterphenyls in 1968. The blood concentrations of these congeners in patients with Yusho remain extremely elevated 50 years after onset. Dioxins exert their toxicity via aryl hydrocarbon receptor (AHR) through the generation of reactive oxygen species (ROS). In this review article, we discuss the pathogenic implication of AHR in dioxin-induced health hazards. We also mention the potential therapeutic use of herbal drugs targeting AHR and ROS in patients with Yusho.
Topics: Animals; Dioxins; Humans; Porphyrias; Reactive Oxygen Species; Receptors, Aryl Hydrocarbon; Rice Bran Oil
PubMed: 33445793
DOI: 10.3390/ijms22020708 -
International Journal of Molecular... Jun 2019Dioxins are ubiquitous and persistent environmental contaminants whose background levels are still reason for concern. There is mounting evidence from both... (Review)
Review
Dioxins are ubiquitous and persistent environmental contaminants whose background levels are still reason for concern. There is mounting evidence from both epidemiological and experimental studies that paternal exposure to the most potent congener of dioxins, 2,3,7,8-tetrachlorodibenzo--dioxin (TCDD), can lower the male/female ratio of offspring. Moreover, in laboratory rodents and zebrafish, TCDD exposure of parent animals has been reported to result in reduced reproductive performance along with other adverse effects in subsequent generations, foremost through the paternal but also via the maternal germline. These impacts have been accompanied by epigenetic alterations in placenta and/or sperm cells, including changes in methylation patterns of imprinted genes. Here, we review recent key studies in this field with an attempt to provide an up-to-date picture of the present state of knowledge to the reader. These studies provide biological plausibility for the potential of dioxin exposure at a critical time-window to induce epigenetic alterations across multiple generations and the significance of aryl hydrocarbon receptor (AHR) in mediating these effects. Currently available data do not allow to accurately estimate the human health implications of these findings, although epidemiological evidence on lowered male/female ratio suggests that this effect may take place at realistic human exposure levels.
Topics: Animals; Biomarkers; Dioxins; Environmental Pollutants; Environmental Pollution; Epigenesis, Genetic; Female; Humans; Male; Maternal Exposure; Maternal Inheritance; Paternal Inheritance; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 31212893
DOI: 10.3390/ijms20122947 -
Environment International Jul 2021Polybrominated dibenzo-p-dioxins and furans (PBDD/Fs) are emerging persistent organic pollutants (POPs) that have similar or higher toxicities than the notorious... (Review)
Review
Polybrominated dibenzo-p-dioxins and furans (PBDD/Fs) are emerging persistent organic pollutants (POPs) that have similar or higher toxicities than the notorious dioxins. Toxicities, formation mechanisms, and environmental fates of PBDD/Fs are lacking because accurate quantification, especially of higher brominated congeners, is challenging. PBDD/F analysis is difficult because of photolysis and thermal degradation and interference from polybrominated diphenyl ethers. Here, literatures on PBDD/F analysis and environmental occurrences are reviewed to improve our understanding of PBDD/F environmental pollution and human exposure levels. Although PBDD/Fs behave similarly to dioxins, different congener profiles between PBDD/Fs and dioxins in the environment indicates their different sources and formation mechanisms. Herein, potential sources and formation mechanisms of PBDD/Fs were critically discussed, and current knowledge gaps and future directions for PBDD/F research are highlighted. An understanding of PBDD/F formation pathways will allow for development of synergistic control strategies for PBDD/Fs, dioxins, and other dioxin-like POPs.
Topics: Dibenzofurans; Dioxins; Environmental Monitoring; Humans; Polychlorinated Dibenzodioxins
PubMed: 33684732
DOI: 10.1016/j.envint.2021.106450 -
Environmental Research Mar 2022Ambient dioxin exposure from industrial sources, excluding exposures from occupations and accidental releases/contamination, may be associated with risk of developing...
Ambient dioxin exposure from industrial sources, excluding exposures from occupations and accidental releases/contamination, may be associated with risk of developing hepatocellular carcinoma (HCC). The objective of this study was to examine the association between county-level ambient dioxin air emissions from industrial sources and HCC risk in the US. We obtained information on 90,359 incident HCC cases diagnosed between 2000 and 2016 from population-based cancer registries across the US in the Surveillance, Epidemiology, and End Results (SEER) database. Dioxin emissions from 1987 to 2007 from a nationwide spatial database of historical dioxin-emitting facilities were linked to the SEER county of residence at diagnosis using a geographic information system (GIS). Poisson regression with robust variance estimation was used to calculate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the association between county-level dioxin emissions and HCC rates adjusting for individual-level age at diagnosis, sex, race/ethnicity, year of diagnosis, SEER registry, and county-level information on health conditions, lifestyle factors, and socioeconomic status. There was no association between dioxin emissions based on the number of dioxin-emitting facilities within a county or average annual emissions within a county and HCC risk. In analyses by facility type, there were positive associations between county-level dioxin emissions from coal-fired power plants (adjusted IRR 1.09, 95% CI 1.01-1.17), but not with the number of these facilities. Similarly, positive associations for industrial boilers and sewage sludge incinerators were evident, but not consistent across both exposure metrics. Future research should incorporate individual-level data to further explore the findings suggested by these ecologic analyses.
Topics: Carcinoma, Hepatocellular; Dioxins; Humans; Incidence; Incineration; Liver Neoplasms; United States
PubMed: 34800530
DOI: 10.1016/j.envres.2021.112386 -
Environment International Feb 2021The insulin-like growth factor (IGF) system is a critical regulator of growth, especially during fetal development, while also playing a central role in metabolic... (Review)
Review
The insulin-like growth factor (IGF) system is a critical regulator of growth, especially during fetal development, while also playing a central role in metabolic homeostasis. Endocrine disruptors (EDs) are ubiquitous compounds able to interfere with hormone action and impact human health. For example, exposure to EDs is associated with decreased birthweight and increased incidence of metabolic disorders. Therefore, the IGF system is a potential target for endocrine disruption. This review summarises the state of the science regarding effects of exposure to major classes of endocrine disruptors (dioxins and dioxin-like compounds, polycyclic aromatic hydrocarbons, polybrominated diphenyl ethers, phthalates, perfluoroalkyl substances and bisphenol A) on the IGF system. Evidence from both experimental models (in vitro and in vivo) and epidemiological studies is presented. In addition, possible molecular mechanisms of action and effects on methylation are discussed. There is a large body of evidence supporting the link between dioxins and dioxin-like compounds and IGF disruption, but mixed findings have been reported in human studies. On the other hand, although only a few animal studies have investigated the effects of phthalates on the IGF system, their negative association with IGF levels and methylation status has been more consistently reported in humans. For polybrominated diphenyl ethers, perfluoroalkyl substances and bisphenol A the evidence is still limited. Despite a lack of studies for some ED classes linking ED exposure to changes in IGF levels, and the need for further research to improve reproducibility and determine the degree of risk posed by EDs to the IGF system, this is clearly an area of concern.
Topics: Animals; Dioxins; Endocrine Disruptors; Halogenated Diphenyl Ethers; Humans; Reproducibility of Results; Somatomedins
PubMed: 33348104
DOI: 10.1016/j.envint.2020.106311 -
International Journal of Molecular... Mar 2020Dioxins and related compounds are common environmental contaminants. Although their levels have gone down, they are still of concern, in particular regarding...
Dioxins and related compounds are common environmental contaminants. Although their levels have gone down, they are still of concern, in particular regarding developmental toxicity. The adverse effects of these compounds are mediated by the aryl hydrocarbon receptor (AHR), whose canonical signaling pathway has been unveiled in fair detail. The alternative (non-genomic) pathways are much more obscure. AHR has also proven to be a master regulator of numerous physiological phenomena, which has led to the search of selective AHR modulators with low toxicity. Papers of this Special Issue address the developmental toxicity of dioxins and related compounds as well as selective modulators of AHR and both its canonical and alternative signaling pathways. In addition, new optical and stereoscopic methods for the detection of dioxins are presented. As a whole, this Special Issue provides an up-to-date view on a wide variety of aspects related to dioxin toxicity mechanisms from both original research articles and reviews.
Topics: Animals; Dioxins; Environmental Pollutants; Humans; Receptors, Aryl Hydrocarbon; Signal Transduction
PubMed: 32231017
DOI: 10.3390/ijms21072342