In adults zebrafish various hepatotoxic compounds inducing three different liver toxic phenotypes
Ontology highlight
ABSTRACT:
ORGANISM(S): Danio rerio
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PROVIDER: S-DIXA-087 | biostudies-other |
REPOSITORIES: biostudies-other
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| S-DIXA-086 | biostudies-other
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| S-DIXA-085 | biostudies-other
Project description:The per-and polyfluoroalkyl substances (PFAS) are of significant global concern due to their highly ubiquitous and persistent nature, bioaccumulation in organisms, and potential toxicity. The aquatic environment is known as an important sink for PFAS resulting in high concentrations in aquatic organisms. However, little is known about the developmental windows of sensitivity in which the PFAS chemicals are biologically active, in addition to the toxicity endpoints that best reflect chemical hazard. In this study, zebrafish (Danio rerio) were exposed to a 0.33% DMSO vehicle control, 1uM chlorpyrifos (CAS 2921-88-2) positive control, and eight concentrations (0-100 uM, half-log dilutions) of three environmentally relevant PFAS compounds in concentration-response: PFOS (CAS 1763-21-1), PFOA (CAS 45285-51-6), and PFHxS (CAS 355-46-4). There was also a group of unexposed zebrafish aliquoted from a single pool into all exposure plates to serve as a quality assurance measure. The goal of this study was to generate transcriptomic point of departure (tPOD; a benchmark dose/concentration -based treatment level below which a concerted gene expression response is not observed) estimates for zebrafish exposed to PFAS compounds as a health protective exposure level for risk assessment. Through the use of short-term embryo/larval plate-based high-throughput toxicity tests, tPODs were determined across seven distinct developmental windows (6-24 hours post fertilization (hpf), 6-48 hpf, 24-48 hpf, 6-120 hpf, 24-120 hpf, 48-120 hpf, 96-120 hpf) to assess how common experimental design variables (e.g., different exposure durations, exposure at different developmental stages) affect point of departure estimates.
2024-08-28 | GSE242402 | GEO
Project description:Rat has been treated with different compounds with the purpose of investigating toxicological mechanisms. But toxic and non-toxic compounds has been administered. 3 toxic (ANIT, DMN, NMF) 3 non-tox (Caerulein, dinitrophenol(DNP), Rosiglitazone) in 5-plicates (30 arrays in all) and 9 untreated (control), 39 samples in all. The array data was used to identify genes with biomarker potential for detecting toxic properties of compounds. Keywords: other
2006-08-12 | GSE5509 | GEO
Project description:Rat has been treated with different compounds with the purpose of investigating toxicological mechanisms. But toxic and non-toxic compounds has been administered. 3 toxic (ANIT, DMN, NMF) 3 non-tox (Caerulein, dinitrophenol(DNP), Rosiglitazone) in 5-plicates (30 arrays in all) and 9 untreated (control), 39 samples in all. The array data was used to identify genes with biomarker potential for detecting toxic properties of compounds. Keywords: other Rats was treated with different compounds and RNA from liver was extracyed after 48 hours. Microarrays (GeneChip Rat230 version 2) was run on the RNA
2006-08-11 | E-GEOD-5509 | biostudies-arrayexpress
Project description:The data currently described was generated within the EU/FP7 HeCaToS project (Hepatic and Cardiac Toxicity Systems modeling). The project aimed to develop an in silico prediction system to contribute to drug safety assessment for humans. For this purpose, multi-omics data of repeated dose toxicity were obtained for 10 hepatotoxic and 10 cardiotoxic compounds. Most data were gained from in vitro experiments in which 3D microtissues (either hepatic or cardiac) were exposed to a therapeutic (physiologically relevant concentrations calculated through PBPK-modeling) or a toxic dosing profile (IC20 after 7 days). Exposures lasted for 14 days and samples were obtained at 7 time points (therapeutic doses: 2-8-24-72-168-240-336 h; toxic doses 0-2-8-24-72-168-240 h). Transcriptomics (RNA sequencing & microRNA sequencing), proteomics (LC-MS), epigenomics (MeDIP sequencing) and metabolomics (LC-MS & NMR) data were obtained from these samples. Furthermore, functional endpoints (ATP content, Caspase3/7 and O2 consumption) were measured in exposed microtissues. Additionally, multi-omics data from human biopsies from patients are available. This data is now being released to the scientific community through the BioStudies data repository ( https://www.ebi.ac.uk/biostudies/ ).
| S-EPMC9663581 | biostudies-literature
Project description:Meckel syndrome, nephronophthisis, Joubert syndrome and Bardet-Biedl syndrome are caused by mutations in proteins that localize to the ciliary transition zone (TZ). The phenotypically distinct syndromes suggest that these TZ proteins have differing functions. However, mutations in a single TZ gene can result in multiple syndromes, suggesting that the phenotype is influenced by modifier genes. We performed a comprehensive analysis of ten zebrafish TZ mutants, including mks1, tmem216, tmem67, rpgrip1l, cc2d2a, b9d2, cep290, tctn1, nphp1 and nphp4, as well as mutants in ift88 and ift172. Our data indicate that variations in phenotypes exist between different TZ mutants, supporting different tissue-specific functions of these TZ genes. Further, we observed phenotypic variations within progeny of a single TZ mutant, reminiscent of multiple disease syndromes being associated with mutations in one gene. In some mutants, the dynamics of the phenotype became complex with transitory phenotypes that are corrected over time. We also demonstrated that multiple-guide-derived CRISPR/Cas9 F0 'crispant' embryos recapitulate zygotic null phenotypes, and rapidly identified ciliary phenotypes in 11 cilia-associated gene candidates (ankfn1, ccdc65, cfap57, fhad1, nme7, pacrg, saxo2, c1orf194, ttc26, zmynd12 and cfap52).
| S-EPMC9844136 | biostudies-literature
Project description:Different animal behavioral phenotypes maintained and selectively bred over multiple generations may be underscored by dissimilar gut microbial community compositions or not have any significant dissimilarity in community composition. Operating within the microbiota-gut-brain axis framework, we anticipated differences in gut microbiome profiles between zebrafish (Danio rerio) selectively bred to display the bold and shy personality types. This would highlight gut microbe-mediated effects on host behavior. To this end, we amplified and sequenced a fragment of the 16S rRNA gene from the guts of bold and shy zebrafish individuals (n=10) via Miseq. We uncovered no significant difference in within-group microbial diversity nor between-group microbial community composition of the two behavioral phenotypes. Interestingly, though not statistically different, we determined that the gut microbial community of the bold phenotype was dominated by Burkholderiaceae, Micropepsaceae, and Propionibacteriaceae. In contrast, the shy phenotype was dominated by Beijerinckaceae, Pirelullacaeae, Rhizobiales_Incertis_Sedis, and Rubinishaeraceae. The absence of any significant difference in gut microbiota profiles between the two phenotypes would suggest that in this species, there might exist a stable "core" gut microbiome, regardless of behavioral phenotypes, and or possibly, a limited role for the gut microbiota in modulating this selected-for host behavior. This is the first study to characterize the gut microbial community of distinct innate behavioral phenotypes of the zebrafish (that are not considered dysbiotic states) and not rely on antibiotic or probiotic treatments to induce changes in behavior. Such studies are crucial to our understanding of the modulating impacts of the gut microbiome on normative animal behavior.
| S-EPMC11160693 | biostudies-literature
Project description:ImportanceUse of herbal and dietary supplements (HDSs) accounts for an increasing proportion of drug hepatotoxicity cases. Turmeric or curcumin, green tea extract, Garcinia cambogia, black cohosh, red yeast rice, and ashwagandha are the most frequently reported hepatoxic botanicals, but their prevalence and reasons for use in the general population are unknown.ObjectiveTo assess the prevalence and clinical characteristics of adult consumers of 6 potentially hepatoxic botanicals.Design, setting, and participantsThis survey study analyzed nationally representative data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative, cross-sectional survey of the general US population. Prescription drug and HDS exposure data in the past 30 days were analyzed, and 2020 US Census data were used for population estimates. Data were analyzed July 1, 2023, to February 1, 2024.ExposuresAdult NHANES participants enrolled between January 2017 and March 2020.Main outcomes and measuresBaseline weighted characteristics of HDS users and users of 6 potentially hepatotoxic botanical products were compared with non-HDS users. Multivariable analysis was undertaken to identify factors associated with HDS use or at-risk botanical use.ResultsAmong 9685 adults enrolled in this NHANES cohort, the mean (SE) age was 47.5 (0.5) years, and 51.8% (95% CI, 50.2%-53.4%) were female. The overall prevalence of HDS product use was 57.6% (95% CI, 55.9%-59.4%), while the prevalence of using the 6 botanicals of interest was 4.7% (95% CI, 3.9%-5.7%). Turmeric-containing botanicals were most commonly used (n = 236), followed by products containing green tea (n = 92), ashwagandha (n = 28), Garcinia cambogia (n = 20), red yeast rice (n = 20), and black cohosh (n = 19). Consumers of these 6 botanicals were significantly older (adjusted odds ratio [AOR], 2.36 [95% CI, 1.06-5.25]; P = .04 for 40-59 years of age and AOR, 3.96 [95% CI, 1.93-8.11]; P = .001 for ≥60 years of age), had a higher educational level (AOR, 4.78 [95% CI, 2.62-8.75]; P < .001), and were more likely to have arthritis (AOR, 2.27 [95% CI, 1.62-3.29]; P < .001) compared with non-HDS users. An estimated 15 584 599 (95% CI, 13 047 571-18 648 801) US adults used at least 1 of the 6 botanical products within the past 30 days, which was similar to the estimated number of patients prescribed potentially hepatotoxic drugs, including simvastatin (14 036 024 [95% CI, 11 202 460-17 594 452]) and nonsteroidal anti-inflammatory drugs (14 793 837 [95% CI, 13 014 623-16 671 897]). The most common reason for consuming turmeric and green tea was to improve or maintain health.Conclusions and relevanceIn this survey study, an estimated 15.6 million US adults consumed at least 1 botanical product with liver liability within the past 30 days, comparable with the number of people who consumed nonsteroidal anti-inflammatory drugs and a commonly prescribed hypolipidemic drug. Given a lack of regulatory oversight on the manufacturing and testing of botanical products, clinicians should be aware of possible adverse events from consumption of these largely unregulated products.
| S-EPMC11301549 | biostudies-literature
Project description:Francisella spp. are facultative intracellular pathogens identified in increasingly diverse hosts, including mammals. F. noatunensis subsp. orientalis and F. noatunensis subsp. noatunensis infect fish inhabiting warm and cold waters, respectively, while F. tularensis subsp. novicida is highly infectious for mice and has been widely used as a model for the human pathogen F. tularensis. Here, we established zebrafish embryo infection models of fluorescently labeled F. noatunensis subsp. noatunensis, F. noatunensis subsp. orientalis, and F. tularensis subsp. novicida at 22, 28, and 32°C, respectively. All infections led to significant bacterial growth, as shown by reverse transcription-quantitative PCR (RT-qPCR), and to a robust proinflammatory immune response, dominated by increased transcription of tumor necrosis factor alpha (TNF-?) and interleukin-1? (IL-1?). F. noatunensis subsp. orientalis was the most virulent, F. noatunensis subsp. noatunensis caused chronic infection, and F. tularensis subsp. novicida showed moderate virulence and led to formation of relatively small granuloma-like structures. The use of transgenic zebrafish strains with enhanced green fluorescent protein (EGFP)-labeled immune cells revealed their detailed interactions with Francisella species. All three strains entered preferentially into macrophages, which eventually assembled into granuloma-like structures. Entry into neutrophils was also observed, though the efficiency of this event depended on the route of infection. The results demonstrate the usefulness of the zebrafish embryo model for studying infections caused by different Francisella species at a wide range of temperatures and highlight their interactions with immune cells.
| S-EPMC4019159 | biostudies-literature