Dataset of liver proteins changed in eu- and hypothyroid female rats upon in vivo exposure to hexabromocyclododecane (HBCD).
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ABSTRACT:
SUBMITTER: Miller I
PROVIDER: S-EPMC4781926 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Male Wistar rats with different thyroid status (eu-, hypothyroid) were exposed to 0, 3 or 30 mg/kg body weight of the flame retardant HBCD for 7 days and obtained data compared with a previous study in females, "Hexabromocyclododecane (HBCD) induced changes in the liver proteome of eu- and hypothyroid female rats" (Miller et al., 2016) [1]. Specifically, proteomic investigation of liver protein patterns obtained by 2D-DIGE was performed and differences between animals groups recorded, based on the factors exposure, thyroid status and gender. All proteins with significantly changed abundance in any of these comparisons were identified by mass spectrometry. General, hormone and proteomic data of both the present and the previous studies are discussed in Miller et al. (2016) [1] and in "Gender specific differences in the liver proteome of rats exposed to hexabromocyclododecane (HBCD)" Miller et al. (2016) [2].
| S-EPMC4992036 | biostudies-literature
Project description:To identify liver transcripts differentially expressed due to treatment with 1,3,5,7,9,11-hexabromocyclododecane (HBCD), we collected RNA from male Harlan Sprague Dawley rats exposed to 0, 0.06, 0.641, 6.41, 64.1 or 641 mg/kg HBCD, 5 days after exposure for animals 7 weeks of age. These samples were interrogated with the Affymetrix Rat Genome 230 2.0 GeneChip array. A total of 1,2,1,23, and 247 gene transcripts were differentially expressed due to HBCD treatment after exposure to 0.06, 0.641, 6.41, 64.1 or 641 mg/kg HBCD (false discovery rate (FDR) < 0.05).
2020-07-15 | GSE153357 | GEO
Project description:The influence of short term (7-day) exposure of male rats to the brominated flame retardant hexabromocyclododecane (HBCD) was studied by investigation of the liver proteome, both in euthyroid and hypothyroid rats and by comparing results with general data on animal physiology and thyroid hormone, leptin, insulin and gonadotropin concentrations determined in parallel. Proteome analysis of liver tissue by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) revealed that only small protein pattern changes were induced by exposure in males, on just a few proteins with different functions and not involved in pathways in common. This is in contrast to previous findings in similarly exposed eu- and hypothyroid female rats, where general metabolic pathways had been shown to be affected. The largest gender-dependent effects concerned basal concentrations of liver proteins already in control and hypothyroid animals, involving mainly the pathways which were also differently affected by HBCD exposure. Among them were differences in lipid metabolism, which - upon exposure to HBCD - may also be the reason for the considerably higher ratio of ?-HBCD accumulated in white adipose tissue of exposed female rats compared to males. The results further elucidate the already suggested different sensitivity of genders towards HBCD exposure on the protein level, and confirm the need for undertaking toxicological animal experiments in both genders.
| S-EPMC6062380 | biostudies-literature
Project description:Hepatic transcriptomic alterations for 1,3,5,7,9,11-hexabromocyclododecane (HBCD) after 5-day exposure in rats
| PRJNA642145 | ENA
Project description:AimApply a recently developed expert elicitation procedure to evaluate the state of the current knowledge of the two brominated flame retardants (BFRs) most commonly used today; decabromo-diphenyl ether (decaBDE) and hexabromocyclododecane (HBCD) and their potential impact on human health in order to support policy considerations. This expert elicitation was organized by the HENVINET (Health and Environment Network) Consortium.MethodThe HENVINET expert elicitation procedure that was used in the evaluations of decaBDE and HBCD is a rapid assessment tool aimed at highlighting areas of agreement and areas of disagreement on knowledge-related key issues for environment and health policy decision making.ResultsThe outcome of the expert consultation on BFRs was concrete expert advice for policy makers with specific priorities for further action made clear for both stakeholders and policy makers. The experts were not in agreement whether or not the knowledge currently available on decaBDE or HBCD is sufficient to justify policy actions, but most experts considered that enough data already exists to support a ban or restriction on the use of these compounds. All experts agreed on the necessity of more research on the compounds. Priority issues for further research were, among others:• more studies on the extent of human exposure to the compounds.• more studies on the fate and concentration in the human body of the compounds.
| S-EPMC3388476 | biostudies-literature
Project description:BackgroundHexabromocyclododecane (HBCD) is a high production volume brominated flame retardant added to building insulation foams, electronics, and textiles. HBCD is a commercial mixture (CM-HBCD) composed of three main stereoisomers: α-HBCD (10%), β-HBCD (10%), and γ-HBCD (80%). A shift from the dominant stereoisomer γ-HBCD to α-HBCD is detected in humans and wildlife.ObjectivesConsidering CM-HBCD has been implicated in neurodevelopment and endocrine disruption, with expected metabolism perturbations, we performed metabolomics on mice serum obtained during a window-of-developmental neurotoxicity to draw correlations between early-life exposures and developmental outcomes and to predict health risks.MethodsSix female C57BL/6 mice at postnatal day (PND) 10 were administered a single gavage dose of α-, γ-, or CM-HBCD at 3, 10, and 30 mg/kg. Nuclear magnetic resonance metabolomics was used to analyze 60 μL serum aliquots of blood collected 4 days post-oral exposure.ResultsInfantile mice exposed to α-, γ-, or CM-HBCD demonstrated differences in endogenous metabolites by treatment and dose groups, including metabolites involved in glycolysis, gluconeogenesis, lipid metabolism, citric acid cycle, and neurodevelopment. Ketone bodies, 3-hydroxybutyrate, and acetoacetate, were nonstatistically elevated, when compared with mean control levels, in all treatment and dose groups, while glucose, pyruvate, and alanine varied. Acetoacetate was significantly increased in the 10 mg/kg α-HBCD and was nonsignificantly decreased with CM-HBCD. A third ketone body, acetone, was significantly lower in the 30 mg/kg α-HBCD group with significant increases in pyruvate at the same treatment and dose group. Metabolites significant in differentiating treatment and dose groups were also identified, including decreases in amino acids glutamate (excitatory neurotransmitter in learning and memory) and phenylalanine (neurotransmitter precursor) after α-HBCD and γ-HBCD exposure, respectively.ConclusionsWe demonstrated that 4 days following a single neonatal oral exposure to α-, γ-, and CM-HBCD resulted in different serum metabolomic profiles, indicating stereoisomer- and mixture-specific effects and possible mechanisms of action.
| S-EPMC5381977 | biostudies-literature
Project description:Hexabromocyclododecane (HBCD) is a brominated flame retardant that presents a threat to aquatic organisms as it can be maternally transferred and has been reported to hinder development and survival in early-life stage (ELS) fish. However, little is known to date regarding the molecular mechanisms that drive the toxicity of HBCD. This study examined the apical and molecular response patterns of maternally transferred HBCD in fathead minnow (Pimephales promelas) larvae at seven (whole transcriptome) and 14 (apical and physiological) days post-fertilization. The larvae sampled at 7dpf for whole transcriptomics analysis revealed dysregulation of pathways involved in membrane integrity (inhibition of calcium channel) and metabolic processes (downregulation of amino acid, glucose, and lipid biosynthesis), while the larvae reared for 14 days exhibited a significant decrease in survival at the highest treatment condition. These results indicate that maternal transfer of HBCD is of concern in fish, which may act through indirect mechanisms involving the inhibition of membrane transport leading to disruption in metabolic processes, collectively resulting in energy depletion and subsequently mortality.
2022-09-02 | GSE212295 | GEO
Project description:The brominated flame retardant, hexabromocyclododecane (HBCD), is added-but not bound-to consumer products and is eventually found in the environment and human tissues. Commercial-grade HBCD mixtures contain three major stereoisomers, alpha (α), beta (β), and gamma (γ), that are typically at a ratio of 12%:6%:82%, respectively. Although HBCD is widely used, the toxicological effects from its exposure in humans are not clearly understood. Using a physiologically based pharmacokinetic (PBPK) model could help improve our understanding of the toxicity of HBCD. The aim of this work was to develop a PBPK model, consisting of five permeability limited compartments (i.e., brain, liver, adipose tissue, blood, and rest of the body), to evaluate the pharmacokinetics of γ-HBCD in C57BL/6 mice. Physiological parameters related to body size, organ weights, and blood flow were taken from the literature. All partition coefficients were calculated based on the log Kow. The elimination in urine and feces was optimized to reflect the percent dose eliminated, as published in the literature. Compared with data from the literature for brain, liver, blood, and adipose tissue, the model simulations accurately described the mouse data set within 1.5-fold of the data points. Also, two examples showing the utility of the PBPK model supplement the information regarding the internal dose that caused the health effects observed during these studies. Although this version of the PBPK model expressly describes γ-HBCD, more efforts are needed to clarify and improve the model to discriminate between the α, β, and γ stereoisomers.
| S-EPMC8674938 | biostudies-literature
Project description:Chronic stress produces long-term metabolic changes throughout the superfamily of nuclear receptors, potentially causing various pathologies. Sex hormones modulate the stress response and generate a sex-specific age-dependent metabolic imprint, especially distinct in the reproductive senescence of females. We monitored chronic stress recovery in two age groups of female Sprague Dawley rats to determine whether stress and/or aging structurally changed the glycolipid microenvironment, a milieu playing an important role in cognitive functions. Old females experienced memory impairment even at basal conditions, which was additionally amplified by stress. On the other hand, the memory of young females was not disrupted. Stress recovery was followed by a microglial decrease and an increase in astrocyte count in the hippocampal immune system. Since dysfunction of the brain immune system could contribute to disturbed synaptogenesis, we analyzed neuroplastin expression and the lipid environment. Neuroplastin microenvironments were explored by analyzing immunofluorescent stainings using a newly developed Python script method. Stress reorganized glycolipid microenvironment in the Cornu Ammonis 1 (CA1) and dentate gyrus (DG) hippocampal regions of old females but in a very different fashion, thus affecting neuroplasticity. The postulation of four possible neuroplastin environments pointed to the GD1a ganglioside enrichment during reproductive senescence of stressed females, as well as its high dispersion in both regions and to GD1a and GM1 loss in the CA1 region. A specific lipid environment might influence neuroplastin functionality and underlie synaptic dysfunction triggered by a combination of aging and chronic stress.
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Project description:Evidence for immune/neuroimmune disturbances as a possible root cause of a range of disorders, including neurodevelopmental disorders, is growing. Although prenatal alcohol exposure (PAE) impacts immune function, few studies to date have examined immune function in relation to long-term negative health outcomes following PAE, and most have focused on males. To fill this gap, we utilized a rat model to examine the effects of PAE on immune/neuroimmune function during early-life [postnatal day 1 (P1), P8, and P22] in PAE and control females. Due to the extensive interplay between the immune and endocrine systems, we also measured levels of corticosterone and corticosterone binding globulin (CBG). While corticosterone levels were not different among groups, CBG levels were lower in PAE offspring from P1 to P8, suggesting a lower corticosterone reservoir that may underlie susceptibility to inflammation. Spleen weights were increased in PAE rats on P22, a marker of altered immune function. Moreover, we detected a unique cytokine profile in PAE compared to control offspring on P8 - higher levels in the PFC and hippocampus, and lower levels in the hypothalamus and spleen. The finding of a specific immune signature in PAE offspring during a sensitive developmental period has important implications for understanding the basis of long-term immune alterations and health outcomes in children with Fetal Alcohol Spectrum Disorder (FASD). Our findings also highlight the future possibility that immune-based intervention strategies could be considered as an adjunctive novel therapeutic approach for individuals with FASD.
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