scholarly journals Lipophilic chemical exposure as a cause of cardiovascular disease

2013 ◽  
Vol 6 (2) ◽  
pp. 55-62 ◽  
Author(s):  
Harold I. Zeliger
Keyword(s):  
Cardiovascular Disease ◽  
Developmental Disorders ◽  
Metabolic Disorders ◽  
Chemical Properties ◽  
Chemical Exposure ◽  
Environmental Chemicals ◽  
Low Molecular Weight ◽  
Endocrine Disorders ◽  
Environmental Chemical

Abstract Environmental chemical exposure has been linked to numerous diseases in humans. These diseases include cancers; neurological and neurodegenerative diseases; metabolic disorders including type 2 diabetes, metabolic syndrome and obesity; reproductive and developmental disorders; and endocrine disorders. Many studies have associated the link between exposures to environmental chemicals and cardiovascular disease (CVD). These chemicals include persistent organic pollutants (POPs); the plastic exudates bisphenol A and phthalates; low molecular weight hydrocarbons (LMWHCs); and poly nuclear aromatic hydrocarbons (PAHs). Here it is reported that though the chemicals reported on differ widely in chemical properties and known points of attack in humans, a common link exists between them. All are lipophilic species that are found in serum. Environmentally induced CVD is related to total lipophilic chemical load in the blood. Lipophiles serve to promote the absorption of otherwise not absorbed toxic hydrophilic species that promote CVD.

scholarly journals Environmental Chemical Diethylhexyl Phthalate Alters Intestinal Microbiota Community Structure and Metabolite Profile in Mice

mSystems ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Ming Lei ◽  
Rani Menon ◽  
Sara Manteiga ◽  
Nicholas Alden ◽  
Carrie Hunt ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Neurodevelopmental Disorders ◽  
Developmental Disorders ◽  
Chemical Exposure ◽  
Metabolite Profile ◽  
Environmental Chemicals ◽  
Toxic Metabolite ◽  
Environmental Chemical ◽  
Diethylhexyl Phthalate

ABSTRACT Exposure to environmental chemicals during windows of development is a potentially contributing factor in gut microbiota dysbiosis and linked to chronic diseases and developmental disorders. We used a community-level model of microbiota metabolism to investigate the effects of diethylhexyl phthalate (DEHP), a ubiquitous plasticizer implicated in neurodevelopmental disorders, on the composition and metabolite outputs of gut microbiota in young mice. Administration of DEHP by oral gavage increased the abundance of Lachnoclostridium, while decreasing Clostridium sensu stricto. Addition of DEHP to in vitro-cultured cecal microbiota increased the abundance of Paenibacillus and Lachnoclostridium. Untargeted metabolomics showed that DEHP broadly altered the metabolite profile in the culture. Notably, DEHP enhanced the production of p-cresol while inhibiting butyrate synthesis. Metabolic model-guided correlation analysis indicated that the likely sources of p-cresol are Clostridium species. Monoculture of Lachnoclostridium bolteae confirmed that it is capable of producing p-hydroxyphenylacetic acid, the immediate precursor of p-cresol, and that the species’ growth is enhanced upon DEHP exposure. Taken together, these findings suggest a model where DEHP increases production of p-cresol, a bacterial metabolite linked with neurodevelopmental disorders, by expanding the abundance of species that synthesize the metabolite’s precursor. IMPORTANCE Several previous studies have pointed to environmental chemical exposure during windows of development as a contributing factor in neurodevelopmental disorders and correlated these disorders with microbiota dysbiosis; however, little is known about how the chemicals specifically alter the microbiota to interfere with development. The findings reported in this paper unambiguously establish that a pollutant linked with neurodevelopmental disorders can directly modify the microbiota to promote the production of a potentially toxic metabolite (p-cresol) that has also been correlated with neurodevelopmental disorders. Furthermore, we used a novel modeling strategy to identify the responsible enzymes and bacterial sources of this metabolite. To the best of our knowledge, the present study is the first to characterize the functional consequence of phthalate exposure on a developed microbiota. Our results suggest that specific bacterial pathways could be developed as diagnostic and therapeutic targets against health risks posed by ingestion of environmental chemicals.

scholarly journals Environmental chemical diethylhexyl phthalate alters intestinal microbiota community structure and metabolite profile in mice

2019 ◽  
Author(s):  
Ming Lei ◽  
Rani Menon ◽  
Sara Manteiga ◽  
Nicholas Alden ◽  
Carrie Hunt ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Neurodevelopmental Disorders ◽  
Developmental Disorders ◽  
Chemical Exposure ◽  
Metabolite Profile ◽  
Environmental Chemicals ◽  
Toxic Metabolite ◽  
Environmental Chemical ◽  
Diethylhexyl Phthalate

AbstractExposure to environmental chemicals during windows of development is a potentially contributing factor in gut microbiota dysbiosis, and linked to chronic diseases and developmental disorders. We used a community-level model of microbiota metabolism to investigate the effects of diethylhexyl phthalate (DEHP), a ubiquitous plasticizer implicated in neurodevelopmental disorders, on the composition and metabolite outputs of gut microbiota in young mice. Administration of DEHP by oral gavage increased the abundance ofLachnoclostridum, while decreasingAkkermansia, Odoribacter, andClostridium sensu stricto. Addition of DEHP toin vitrocultured cecal microbiota increased the abundance ofAlistipes, Paenibacillus, andLachnoclostridium. Untargeted metabolomics showed that DEHP broadly altered the metabolite profile in the culture. Notably, DEHP enhanced the production ofp-cresol, while inhibiting butyrate synthesis. Metabolic model-guided correlation analysis indicated that the likely sources ofp-cresol areClostridiumspecies. Our results suggest that DEHP can directly modify the microbiota to affect production of bacterial metabolites linked with neurodevelopmental disorders.ImportanceSeveral previous studies have pointed to environmental chemical exposure during windows of development as a contributing factor in neurodevelopmental disorders, and correlated these disorders with microbiota dysbiosis, little is known about how the chemicals specifically alter the microbiota to interfere with development. The findings reported in this paper unambiguously establish that a pollutant linked with neurodevelopmental disorders can directly modify the microbiota to promote the production of a potentially toxic metabolite (p-cresol) that has also been correlated with neurodevelopmental disorders. Further, we use a novel modeling strategy to identify the responsible enzymes and bacterial sources of this metabolite. To the best of our knowledge, the present study is the first to characterize the functional consequence of phthalate exposure on a developed microbiota. Our results suggest that specific bacterial pathways could be developed as diagnostic and therapeutic targets against health risks posed by ingestion of environmental chemicals.

scholarly journals Multifaceted Physiological Roles of Adiponectin in Inflammation and Diseases

2020 ◽  
Vol 21 (4) ◽  
pp. 1219 ◽  
Author(s):  
Hyung Muk Choi ◽  
Hari Madhuri Doss ◽  
Kyoung Soo Kim
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
Metabolic Disorders ◽  
Serum Levels ◽  
High Serum ◽  
Low Molecular Weight ◽  
High Serum Level ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

Adiponectin is the richest adipokine in human plasma, and it is mainly secreted from white adipose tissue. Adiponectin circulates in blood as high-molecular, middle-molecular, and low-molecular weight isoforms. Numerous studies have demonstrated its insulin-sensitizing, anti-atherogenic, and anti-inflammatory effects. Additionally, decreased serum levels of adiponectin is associated with chronic inflammation of metabolic disorders including Type 2 diabetes, obesity, and atherosclerosis. However, recent studies showed that adiponectin could have pro-inflammatory roles in patients with autoimmune diseases. In particular, its high serum level was positively associated with inflammation severity and pathological progression in rheumatoid arthritis, chronic kidney disease, and inflammatory bowel disease. Thus, adiponectin seems to have both pro-inflammatory and anti-inflammatory effects. This indirectly indicates that adiponectin has different physiological roles according to an isoform and effector tissue. Knowledge on the specific functions of isoforms would help develop potential anti-inflammatory therapeutics to target specific adiponectin isoforms against metabolic disorders and autoimmune diseases. This review summarizes the current roles of adiponectin in metabolic disorders and autoimmune diseases.

scholarly journals Exposure to lipophilic chemicals as a cause of neurological impairments, neurodevelopmental disorders and neurodegenerative diseases

2013 ◽  
Vol 6 (3) ◽  
pp. 103-110 ◽  
Author(s):  
Harold I. Zeliger
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodevelopmental Disorders ◽  
Chemical Properties ◽  
Environmental Chemicals ◽  
Polynuclear Aromatic Hydrocarbons ◽  
Low Molecular Weight ◽  
Hyperactivity Disorder ◽  
Sensory Impairments ◽  
Sequential Absorption ◽  
Lateral Sclerosis

ABSTRACT Many studies have associated environmental exposure to chemicals with neurological impairments (NIs) including neuropathies, cognitive, motor and sensory impairments; neurodevelopmental disorders (NDDs) including autism and attention deficit hyperactivity disorder (ADHD); neurodegenerative diseases (NDGs) including Alzheimer´s disease, Parkinson’s disease and amyotrophic lateral sclerosis (ALS). The environmental chemicals shown to induce all these diseases include persistent organic pollutants (POPs), the plastic exudates bisphenol A and phthalates, low molecular weight hydrocarbons (LMWHCs) and polynuclear aromatic hydrocarbons (PAHs). It is reported here that though these chemicals differ widely in their chemical properties, reactivities and known points of attack in humans, a common link does exist between them. All are lipophilic species found in serum and they promote the sequential absorption of otherwise non-absorbed toxic hydrophilic species causing these diseases.

scholarly journals CLINICAL-METABOLIC AND HORMONAL RELATIONSHIPS BETWEEN PARATHYROID DISEASE AND OTHER NON-CANCEROUS ENDOCRINE DISORDERS IN THE CHORNOBYL NPP ACCIDENT SURVIVORS

2021 ◽  
Vol 26 ◽  
pp. 410-425
Author(s):  
O. Kaminskyi ◽  
◽  
O. Kopylova ◽  
D. Afanasyev ◽  
I. Muraviova ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Vitamin D ◽  
Parathyroid Hormone ◽  
Ionizing Radiation ◽  
Metabolic Disorders ◽  
Strong Association ◽  
Parathyroid Hyperplasia ◽  
Control Group ◽  
Endocrine Disorders ◽  
Exclusion Zone

Objective: to investigate the clinical, hormonal-metabolic and structural features of parathyroid injuries in survivors exposed to ionizing radiation after the Chornobyl NPP accident in adulthood and childhood, both with their connections to other non-cancerous endocrine disorders, and to establish the respective interhormonal and dysmetabolic relationships. Materials and methods. Clinical effects of ionizing radiation on the endocrine system in persons affected by the Chornobyl NPP accident (n = 224) and their descendants (n = 146), compared with the general population sample (n = 70) were the study object. All patients underwent the ultrasound thyroid and parathyroid examination. The generally recognized clinical, anthropometric (body weight, height, thigh volume, body mass index), instrumental (ultrasound examination of thyroid and parathyroid glands), laboratory (biochemical, hormonal), and statistical methods were applied. Parametric and nonparametric statistical methods were used in data processing. The value of p < 0.05 was considered a statistically significant. Results. No significant difference was found in the incidence of carbohydrate metabolic disorders in the Chornobyl NPP (ChNPP) accident consequences clean-up workers (ACCUW), evacuees from the NPP 30-km exclusion zone, residents of radiologically contaminated areas and in the control group in whom the parathyroid hyperplasia was detected. There was a significant increase in the incidence of arterial hypertension among ACCUW who had parathyroid hyperplasia (76.9%) vs. the control group (51.2%). In cases of parathyoid hyperplasia the vitamin D levels were significantly lower than without it. Vitamin D insufficiency/deficiency was found in 94% of the surveyed subjects. The average level of parathyroid hormone in blood serum was significantly higher in the ACCUW of «iodine» period with diagnosed parathyroid hyperplasia than in the control group: (57.2 ± 2.87) pg / ml against (32.74 ± 3.58) pg / ml, p < 0.05. Results of multivariative analysis indicated a strong association of vitamin 25(OH)D insufficiency/deficiency with development of thyroid disease, carbohydrate metabolic disorders, cardiovascular disease, osteopenia/osteoporosis. parathyroid ultrasound scan was at that an effective diagnostic method for primary screening for parathyroid hyperplasia and regular monitoring of the treatment efficiency. When examining children born to parents irradiated after the ChNPPA the parathyroid hyperplasia (58%) and low serum content of vitamin D (11.6 ± 3.5) nmol / l were most often found in children living on radiologically contaminated territories (RCT). A strong correlation was established between the HOMA insulin resistance index and serum content of vitamin D (r = 0.65), parathyroid hormone (r = 0.60), and free thyroxine (r = 0.68) in the group of children born to parents irradiated after the ChNPPA, having got chronic autoimmune thyroiditis, which indicated a relationship between thyroid function, impaired carbohydrate and fat metabolism and the state of parathyroids. Conclusions. No difference in the incidence of carbohydrate metabolic disorders was found in the ChNPP ACCUW, evacuees from the 30-km exclusion zone, and residents of radiologically contaminated territories in whom parathyroid hyperplasia was detected vs. the control group. Patients with parathyroid hyperplasia were found to be defi cient in vitamin D in 94% of cases, and level of latter was significantly lower than under the normal parathyroid size. There was a significant increase in the incidence of diagnosed arterial hypertension among ACCUW who had parathyroid hyperplasia vs. the control group: (76.9 ± 3.5)% vs. (51.2 ± 3.7)%. According to multivariate analysis a strong association between the vitamin 25(OH)D insufficiency/deficiency and development of thyroid disease, carbohydrate metabolic disorders, cardiovascular disease, and osteopenia/osteoporosis was established. The average level of parathyroid hormone in the blood serum of the ChNPP ACCUW of the «iodine» period with diagnosed parathyroid hyperplasia was significantly higher (57.2 ± 2.87) pg / ml against (32.74 ± 3.58) pg / ml; p <0,05) in the control group. Key words: ChNPP accident, irradiation, accident survivors, accident consequences clean-up workers, ionizing radiation, parathyroids, hyperplasia, hyperparathyroidism, thyroid.

scholarly journals PCB126 exposure revealed alterations in m6A RNA modifications in transcripts associated with AHR activation

2020 ◽  
Author(s):  
Neelakanteswar Aluru ◽  
Sibel I Karchner
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Chemical Exposure ◽  
Environmental Chemicals ◽  
Rna Modifications ◽  
Environmental Chemical ◽  
Stop Codons ◽  
Developmental Gene Expression

AbstractChemical modifications of proteins, DNA and RNA moieties play critical roles in regulating gene expression. Emerging evidence suggests these RNA modifications (epitranscriptomics) have substantive roles in basic biological processes. One of the most common modifications in mRNA and noncoding RNAs is N6-methyladenosine (m6A). In a subset of mRNAs, m6A sites are preferentially enriched near stop codons, in 3’ UTRs, and within exons, suggesting an important role in the regulation of mRNA processing and function including alternative splicing and gene expression. Very little is known about the effect of environmental chemical exposure on m6A modifications. As many of the commonly occurring environmental contaminants alter gene expression profiles and have detrimental effects on physiological processes, it is important to understand the effects of exposure on this important layer of gene regulation. Hence, the objective of this study was to characterize the acute effects of developmental exposure to PCB126, an environmentally relevant dioxin-like PCB, on m6A methylation patterns. We exposed zebrafish embryos to PCB126 for 6 hours starting from 72 hours post-fertilization and profiled m6A RNA using methylated RNA immunoprecipitation followed by sequencing (MeRIP-seq). Our analysis revealed 117 and 217 m6A peaks in the DMSO and PCB126 samples (FDR 5%), respectively. The majority of the peaks were preferentially located around the 3’UTR and stop codons. Statistical analysis revealed 15 m6A marked transcripts to be differentially methylated by PCB126 exposure. These include transcripts that are known to be activated by AHR agonists (e.g., ahrra, tiparp, nfe2l2b) as well as others that are important for normal development (vgf, cebpd, foxi1). These results suggest that environmental chemicals such as dioxin-like PCBs could affect developmental gene expression patterns by altering m6A levels. Further studies are necessary to understand the functional consequences of exposure-associated alterations in m6A levels.

scholarly journals PCB126 Exposure Revealed Alterations in m6A RNA Modifications in Transcripts Associated With AHR Activation

2020 ◽  
Author(s):  
Neelakanteswar Aluru ◽  
Sibel I Karchner
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Chemical Exposure ◽  
Environmental Chemicals ◽  
Rna Modifications ◽  
Environmental Chemical ◽  
Stop Codons ◽  
Developmental Gene Expression

Abstract Chemical modifications of proteins, DNA, and RNA moieties play critical roles in regulating gene expression. Emerging evidence suggests the RNA modifications (epitranscriptomics) have substantive roles in basic biological processes. One of the most common modifications in mRNA and noncoding RNAs is N6-methyladenosine (m6A). In a subset of mRNAs, m6A sites are preferentially enriched near stop codons, in 3′ UTRs, and within exons, suggesting an important role in the regulation of mRNA processing and function including alternative splicing and gene expression. Very little is known about the effect of environmental chemical exposure on m6A modifications. As many of the commonly occurring environmental contaminants alter gene expression profiles and have detrimental effects on physiological processes, it is important to understand the effects of exposure on this important layer of gene regulation. Hence, the objective of this study was to characterize the acute effects of developmental exposure to PCB126, an environmentally relevant dioxin-like PCB, on m6A methylation patterns. We exposed zebrafish embryos to PCB126 for 6 h starting from 72 h post fertilization and profiled m6A RNA using methylated RNA immunoprecipitation followed by sequencing (MeRIP-seq). Our analysis revealed 117 and 217 m6A peaks in the DMSO and PCB126 samples (false discovery rate 5%), respectively. The majority of the peaks were preferentially located around the 3′ UTR and stop codons. Statistical analysis revealed 15 m6A marked transcripts to be differentially methylated by PCB126 exposure. These include transcripts that are known to be activated by AHR agonists (eg, ahrra, tiparp, nfe2l2b) as well as others that are important for normal development (vgf, cebpd, sned1). These results suggest that environmental chemicals such as dioxin-like PCBs could affect developmental gene expression patterns by altering m6A levels. Further studies are necessary to understand the functional consequences of exposure-associated alterations in m6A levels.

scholarly journals From Extrapolation to Precision Chemical Hazard Assessment: The Ecdysone Receptor Case Study

Toxics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 6
Author(s):  
Raquel Ruivo ◽  
João Sousa ◽  
Teresa Neuparth ◽  
Olivier Geffard ◽  
Arnaud Chaumot ◽  
...  
Keyword(s):  
Hazard Assessment ◽  
Functional Characterization ◽  
Chemical Exposure ◽  
Environmental Chemicals ◽  
Current Evidence ◽  
Ecdysone Receptor ◽  
Environmental Chemical ◽  
Chemical Action ◽  
Assessment Strategies

Hazard assessment strategies are often supported by extrapolation of damage probabilities, regarding chemical action and species susceptibilities. Yet, growing evidence suggests that an adequate sampling of physiological responses across a representative taxonomic scope is of paramount importance. This is particularly relevant for Nuclear Receptors (NR), a family of transcription factors, often triggered by ligands and thus, commonly exploited by environmental chemicals. Within NRs, the ligand-induced Ecdysone Receptor (EcR) provides a remarkable example. Long regarded as arthropod specific, this receptor has been extensively targeted by pesticides, seemingly innocuous to non-target organisms. Yet, current evidence clearly suggests a wider presence of EcR orthologues across metazoan lineages, with unknown physiological consequences. Here, we address the state-of-the-art regarding the phylogenetic distribution and functional characterization of metazoan EcRs and provide a critical analysis of the potential disruption of such EcRs by environmental chemical exposure. Using EcR as a case study, hazard assessment strategies are also discussed in view of the development of a novel “precision hazard assessment paradigm.

scholarly journals Bisphenol A Is More Potent than Phthalate Metabolites in Reducing Pancreatic β-Cell Function

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Nina Mickelson Weldingh ◽  
Lena Jørgensen-Kaur ◽  
Rune Becher ◽  
Jørn A. Holme ◽  
Johanna Bodin ◽  
...  
Keyword(s):  
Cell Death ◽  
Insulin Secretion ◽  
Bisphenol A ◽  
Cell Function ◽  
Chemical Exposure ◽  
Environmental Chemicals ◽  
Environmental Chemical ◽  
Simultaneous Exposure ◽  
Phthalate Metabolites ◽  
Β Cell Function

Bisphenol A (BPA) and phthalates are common environmental contaminants that have been proposed to influence incidence and development of types 1 and 2 diabetes. Thus, effects of BPA and three phthalate metabolites (monoisobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), and mono-(2-ethylhexyl) phthalate (MEHP)) were studied in the pancreatic β-cell line INS-1E, after 2–72 h of exposure to 5–500 μM. Three endpoints relevant to accelerated development of types 1 or 2 diabetes were investigated: β-cell viability, glucose-induced insulin secretion, and β-cell susceptibility to cytokine-induced cell death. BPA and the phthalate metabolites reduced cellular viability after 72 h of exposure, with BPA as the most potent chemical. Moreover, BPA, MEHP, and MnBP increased insulin secretion after 2 h of simultaneous exposure to chemicals and glucose, with potency BPA > MEHP > MnBP. Longer chemical exposures (24–72 h) showed no consistent effects on glucose-induced insulin secretion, and none of the environmental chemicals affected susceptibility to cytokine-induced cell death. Overall, BPA was more potent than the investigated phthalate metabolites in affecting insulin secretion and viability in the INS-1E pancreatic β-cells. In contrast to recent literature, concentrations with relevance to human exposures (1–500 nM) did not affect the investigated endpoints, suggesting that this experimental model displayed relatively low sensitivity to environmental chemical exposure.

scholarly journals Adverse Impact of Environmental Chemicals on Developmental Origins of Kidney Disease and Hypertension

2021 ◽  
Vol 12 ◽  
Author(s):  
Chien-Ning Hsu ◽  
You-Lin Tain
Keyword(s):  
Kidney Disease ◽  
Animal Studies ◽  
Kidney Development ◽  
Renin Angiotensin System ◽  
Chemical Exposure ◽  
Environmental Chemicals ◽  
Developmental Origins ◽  
Environmental Chemical ◽  
Pregnancy And Lactation ◽  
Exposure During Pregnancy

Chronic kidney disease (CKD) and hypertension are becoming a global health challenge, despite developments in pharmacotherapy. Both diseases can begin in early life by so-called “developmental origins of health and disease” (DOHaD). Environmental chemical exposure during pregnancy can affect kidney development, resulting in renal programming. Here, we focus on environmental chemicals that pregnant mothers are likely to be exposed, including dioxins, bisphenol A (BPA), phthalates, per- and polyfluoroalkyl substances (PFAS), polycyclic aromatic hydrocarbons (PAH), heavy metals, and air pollution. We summarize current human evidence and animal models that supports the link between prenatal exposure to environmental chemicals and developmental origins of kidney disease and hypertension, with an emphasis on common mechanisms. These include oxidative stress, renin-angiotensin system, reduced nephron numbers, and aryl hydrocarbon receptor signaling pathway. Urgent action is required to identify toxic chemicals in the environment, avoid harmful chemicals exposure during pregnancy and lactation, and continue to discover other potentially harmful chemicals. Innovation is also needed to identify kidney disease and hypertension in the earliest stage, as well as translating effective reprogramming interventions from animal studies into clinical practice. Toward DOHaD approach, prohibiting toxic chemical exposure and better understanding of underlying mechanisms, we have the potential to reduce global burden of kidney disease and hypertension.

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