Comparative Glucocorticoid Receptor Agonism: In Silico, In Vitro, and In Vivo and Identification of Potential Biomarkers for Synthetic Glucocorticoid Exposure

Environmental Toxicology and Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Abstract The glucocorticoid receptor (GR) is present in almost every vertebrate cell and utilized many biological processes. Despite an abundance of mammalian data, the structural conservation cross-species susceptibility, particularly for aquatic species, has not been well defined. Efforts to reduce, refine, and/or replace animal testing have increased, driving impetus advance development new approach methodologies (NAMs). Here we used silico, vitro, vivo methods elucidate a greater understanding receptor-mediated effects synthetic exposure teleost fish. Evolutionary amino acid residues critical transcriptional activation was confirmed silico using sequence alignment predict across species susceptibility. Subsequent vitro assays zebrafish human GR provided evidence physiological congruence agonism. Finally, adult fathead minnows (Pimephales promelas) were exposed glucocorticoids, dexamethasone (0.04, 400, 4,000 µg/L) beclomethasone dipropionate (130 µg/L), agonism via digital polymerase chain reaction; addition, EcoToxChip analyses identified potential mRNA biomarkers following exposure. These findings support use NAMs potentially reduce multispecies experimentation while providing empirical that expands taxonomic domain applicability molecular initiating event within broader adverse outcome pathway network.

Language: Английский

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Pesticides in surface freshwater: a critical review

Environmental Monitoring and Assessment, Journal Year: 2022, Volume and Issue: 194(6)

Published: May 24, 2022

Language: Английский

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Effect‐Based Trigger Values Are Essential for the Uptake of Effect‐Based Methods in Water Safety Planning

Environmental Toxicology and Chemistry, Journal Year: 2022, Volume and Issue: 42(3), P. 714 - 726

Published: Dec. 16, 2022

Effect-based methods (EBMs) using in vitro bioassays and well plate-based vivo assays are recommended for water quality monitoring because they can capture the mixture effects of many chemicals present water. Many highly sensitive, so an effect a bioassay does not necessarily indicate poor chemical quality. Consequently, effect-based trigger values (EBTs) have been introduced to differentiate between acceptable unacceptable required wider acceptance EBMs by sector regulatory bodies. These EBTs derived both drinking surface protect human ecological health, respectively, available indicative specific receptor-mediated effects, as adaptive stress responses, apical triggered chemicals. An overview currently is provided, simple approach proposed predict interim without EBT based on concentration assay reference compound. There was good agreement predicted this simplistic from literature more robust methods. Finally, interpretation framework that outlines steps take if sample exceeds developed help facilitate uptake routine safety planning production. Environ Toxicol Chem 2023;42:714-726. © 2022 The Authors. Environmental Toxicology Chemistry published Wiley Periodicals LLC behalf SETAC.

Language: Английский

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Are synthetic glucocorticoids in the aquatic environment a risk to fish?

Environment International, Journal Year: 2022, Volume and Issue: 162, P. 107163 - 107163

Published: Feb. 28, 2022

The glucocorticosteroid, or glucocorticoid (GC), system is largely conserved across vertebrates and plays a central role in numerous vital physiological processes including bone development, immunomodulation, modification of glucose metabolism the induction stress-related behaviours. As result their wide-ranging actions, synthetic GCs are widely prescribed for human veterinary therapeutic purposes consequently have been detected extensively within aquatic environment. Synthetic designed humans pharmacologically active non-mammalian vertebrates, fish, however they generally surface waters at low (ng/L) concentrations. In this review, we assess potential environmental risk to fish by comparing available experimental data effect levels with those mammals. We found majority compounds were predicted insignificant some be moderate high although dataset used analysis was small. Given common mode action level inter-species target conservation exhibited amongst GCs, also give due consideration mixture effects, which may particularly significant when considering impact from class pharmaceuticals. Finally, provide recommendations further research more fully understand relatively understudied group commonly drugs.

Language: Английский

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Global occurrence of synthetic glucocorticoids and glucocorticoid receptor agonistic activity, and aquatic hazards in effluent discharges and freshwater systems

Environmental Pollution, Journal Year: 2023, Volume and Issue: 329, P. 121638 - 121638

Published: April 18, 2023

Language: Английский

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High-Throughput Transcriptomics of Water Extracts Detects Reductions in Biological Activity with Water Treatment Processes

Environmental Science & Technology, Journal Year: 2024, Volume and Issue: 58(4), P. 2027 - 2037

Published: Jan. 18, 2024

The presence of numerous chemical contaminants from industrial, agricultural, and pharmaceutical sources in water supplies poses a potential risk to human ecological health. Current analyses suffer limitations, including coverage high cost, broad-coverage vitro assays such as transcriptomics may further improve quality monitoring by assessing large range possible effects. Here, we used high-throughput assess the activity induced field-derived extracts MCF7 breast carcinoma cells. Wastewater surface largest changes expression among cell proliferation-related genes neurological, estrogenic, antibiotic pathways, whereas drinking reclaimed that underwent advanced treatment showed substantially reduced bioactivity on both gene pathway levels. Importantly, fewer than laboratory blanks, which reinforces previous conclusions based targeted improves confidence bioassay-based quality.

Language: Английский

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Derivation and characterization of environmental hazard concentrations for chemical prioritization: a case study in the Great Lakes tributaries

Environmental Toxicology and Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Ongoing anthropogenic activities and analytical advancements yield continuously expanding lists of environmental contaminants. This represents a challenge to managers, who must prioritize chemicals for management actions (e.g., restriction, regulation, remediation) but are often hindered by resource limitations. To help facilitate prioritization efforts, this study presents several strategies deriving hazard concentrations using publicly accessible data open-source computational tools. Using Great Lakes tributaries aquatic monitoring dataset as case study, were obtained or derived 334 organic chemicals. These based on (1) current water quality guidelines; (2) apical screening values; (3) (4) nonapical effect from the ECOTOXicology Knowledgebase; (5) in vitro ToxCast database; (6) cytotoxic burst collated Comptox Dashboard; (7) "estimated values" modeled estimated available various regulatory nonregulatory agencies; (8) pharmaceutical potency estimates MaPPFAST (9) quantitative structure-activity relationship (QSAR)-derived acute toxicity estimates. Environmental fate included half-lives bioconcentration factors Dashboard QSARs. identify patterns that could be used characterization, availability ecotoxicological evaluated. Furthermore, exceedances evaluated compared across diverse types. Altogether, providing detailed methodology practical examples generated with real data, demonstrated these concentration derivation can efficiently effectively large, complex datasets identified critical considerations future efforts.

Language: Английский

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An assessment of metal concentrations in leaves, roots, and associated sediments of mangrove plant (Avicennia marina) in the Myeik area, Myanmar

Marine Pollution Bulletin, Journal Year: 2025, Volume and Issue: 216, P. 117973 - 117973

Published: April 16, 2025

Language: Английский

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Inhibition of Fin Regeneration in Fathead Minnow (Pimephales promelas) by a Potent Synthetic Glucocorticoid and Development of Adverse Outcome Pathway 334

Environmental Science & Technology, Journal Year: 2025, Volume and Issue: unknown

Published: May 6, 2025

Despite structural and functional conservation across vertebrate species, the glucocorticoid receptor has been minimally studied in comparison to other biological targets for endocrine-disrupting compounds aquatic systems. Because prolonged use of pharmaceutical glucocorticoids humans linked osteoporosis impaired bone growth, we hypothesized that ability teleost fish regenerate fins following damage may be inhibited by exposure synthetic environment. In present study, examined fin regeneration a 7 days waterborne juvenile fathead minnows (Pimephales promelas) glucocorticoids, fluticasone propionate dexamethasone. Expression several biologically relevant gene products (sgk1, tdgf1, runx2a, lef1, shha, tsc22d3) was measured paired caudal whole-body tissues. Fluticasone dexamethasone significantly at water concentrations 2.62 μg/L 4.62 mg/L, respectively. Changes expression indicated disruption intercellular communication Wnt/β-catenin morphogenetic protein (BMP) signaling pathways after 4.86 propionate. Upregulation tsc22d3, transcription factor responsible suppression anti-inflammatory response, plausible cause repressed cellular signaling. These findings advance development adverse outcome pathway 334─Glucocorticoid Receptor Activation Leads Impaired Fin Regeneration─and elucidate both mechanistic relationship between activation inhibition regeneration, which could plausibly reduce individual fitness

Language: Английский

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Effect-based monitoring of two rivers under urban and agricultural influence reveals a range of biological activities in sediment and water extracts

Journal of Environmental Management, Journal Year: 2023, Volume and Issue: 351, P. 119692 - 119692

Published: Nov. 30, 2023

Chemical contaminants, such as pesticides, pharmaceuticals and industrial compounds are ubiquitous in surface water sediment areas subject to human activity. While targeted chemical analysis is typically used for quality monitoring, there growing interest applying effect-based methods with vitro bioassays capture the effects of all active contaminants a sample. The current study evaluated biological from two contrasting catchments Aotearoa New Zealand, highly urbanised Whau River catchment Tāmaki Makaurau (Auckland) urban mixed agricultural Koreti (New River) Estuary catchment. Two complementary passive sampling devices, Chemcatcher polar chemicals polyethylene (PED) non-polar chemicals, were applied wide range water, while composite samples collected at each site. Bioassays indicative induction xenobiotic metabolism, receptor-mediated effects, genotoxicity, cytotoxicity apical extracts. Most extracts induced moderate strong estrogenic aryl hydrocarbon (AhR) activity, along toxicity bacteria. showed similar patterns extracts, but lower Generally, greater photosynthesis inhibition algal growth than PED though AhR observed compared available ecological trigger values (EBT) evaluate potential risk. For most sites both exceeded EBT estrogenicity, many exceeding EBTs activity inhibition. Of endpoints considered, herbicidal appear be primary risk drivers catchments.

Language: Английский

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