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Flutamide treated rat hepatocytes in microfluidic biochips

ABSTRACT: We investigated the effects of the flutamide (FLU) -induced liver injury in primary rat hepatocytes using our liver microfluidic biochips. Flutamide is used a non-steroidal anti-androgenic drug. Two flutamide concentrations, 10µM and 100µM, were used to expose the hepatocytes for 24h under perfusion.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE44317 | GEO | 2013/12/01

SECONDARY ACCESSION(S): PRJNA189450

REPOSITORIES: GEO

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Flutamide treated rat hepatocytes in microfluidic biochips

Project description:We investigated the effects of the flutamide (FLU) -induced liver injury in primary rat hepatocytes using our liver microfluidic biochips. Flutamide is used a non-steroidal anti-androgenic drug. Two flutamide concentrations, 10M-BM-5M and 100M-BM-5M, were used to expose the hepatocytes for 24h under perfusion. Primary rat hepatocytes were cultivated in microfluidic biochips and treated with 10 and 100M-BM-5M of flutamide for 24h

2013-12-01 | E-GEOD-44317 | biostudies-arrayexpress

Transcriptomic effects of endocrine disruptors in zebrafish embryos

2014-03-06 | GSE44263 | GEO

Rattus norvegicus

Project description:Flutamide treated rat hepatocytes in microfluidic biochips

| PRJNA189450 | ENA

Human periodontal ligament fibroblasts (PdLFs) were treated with L-lactic acid, a metabolite from periapical granulomas, in comparison to the untreated and positive controls

Project description:Human PdLFs (iCell Bioscience, China) were treated with 1µM, 10µM, and 100µM L-lactic acid (Sigma-Aldrich, Germany). Phorbol 12-myristate 13-acetate (PMA) (ab120297, Abcam, UK) at 1µM was used as an inflammatory inducer, a positive control for the expression and synthesis of collagen and MMP-1. Untreated PdLFs were regarded as control. PdLFs were incubated at 37°C and 5% CO2 for 2 days and 6 days.

2023-05-31 | E-MTAB-12932 | biostudies-arrayexpress

Human periodontal ligament fibroblasts (PdLFs) were treated with 1-nonadecene, a metabolite from radicular cysts, in comparison to the untreated and positive controls

Project description:Human PdLFs (iCell Bioscience, China) were treated with 1µM, 10µM, and 100µM 1-nonadecene (TCI, US-Japan). PdLFs were treated daily with fresh media containing 1-nonadecene for 2- and 6-days. Phorbol 12-myristate 13-acetate (PMA) (ab120297, Abcam, UK) at 1µM was used as an inflammatory inducer, a positive control for the expression and synthesis of MMP-1, N-cadherin, and as a negative control for the expression of E-cadherin. Untreated PdLFs were regarded as control.

2023-06-09 | E-MTAB-12931 | biostudies-arrayexpress

Transcriptomic effects of endocrine disruptors in zebrafish embryos

Project description:The identification of endocrine disruptive properties of chemicals certain to enter the aquatic environment relies on toxicity tests with fish, assessing adverse effects on reproduction and sexual development. The demand for quick, reliable endocrine disruption (ED) assays favored the use of fish embryos as alternative test organisms. We investigated the application of a transcriptomics-based assay for estrogenic and anti-androgenic chemicals with zebrafish embryos. Two reference compounds, 17a-ethinylestradiol and flutamide, were tested to evaluate the effects on development and the transcriptome after 48h-exposures. Comparison of the transcriptome response with other estrogenic and anti-androgenic compounds (genistein, bisphenol A, methylparaben, linuron, prochloraz, propanil) showed commonalities and differences in regulated pathways, enabling us to classify the estrogenic and anti-androgenic potencies. This demonstrates that different mechanism of ED can be assessed already in fish embryos. Newly fertilized embryos (<2hpf) were exposed for 48 hours to 0.65mg/l (EC10) and 0.8mg/l (EC20) 17-alpha ethinylestradiol (EE2), 1.2mg/l (EC10) and 1.4mg/l (EC20) flutamide, 8 mg/l (EC10)and 8.5mg/l (EC20) bisphenol A(BPA), 0.8 mg/l (EC10) and 1.1mg/l (EC20) propanil, 19.8mg/l (EC10) and 24.4mg/l (EC20) methylparaben, 1.2 mg/l (EC10) and 1.3mg/l (EC20) linuron as well as to 1.7mg/l (EC10) and 2 mg/l (EC20) prochloraz. Water controls were included in all studies and acetone solvent controls were applied when indicated (AC). For each study, four replicates (a,b,c,d) were performed per condition, each consisting of 24 pooled embryos.

2014-03-06 | E-GEOD-44263 | biostudies-arrayexpress

The ureic-based herbicide linuron and the model anti-androgen flutamide regulate common gene networks in the fathead minnow (Pimephales promelas) ovary

Project description:The herbicide linuron is an endocrine disruptor with a suspected anti-androgenic mode of action (MOA) but the complete MOA for LIN is not fully characterized. The objectives of this study were to better characterize the MOA of LIN in the fathead minnow (FHMs) ovary by comparing expression profiles of LIN to dihydrotestosterone (DHT) and flutamide (FLUT), both model compounds with well defined androgenic and anti-androgenic MOAs respectively. Ovarian explants from vitellogenic FHMs were exposed to 10-6 M, 10-7 M, and 10-8 M of DHT, FLUT, and LIN in vitro in a12 hour incubation experiment. Ovary explants exposed to DHT showed a significant increase in E2 production compared to controls but FLUT and LIN did not affect E2 production. Microarray analysis and support vector machine classification revealed that expression patterns of FLUT and LIN in the ovary were more similar to each other compared to DHT and other androgens. Gene set enrichment analysis identified the notch signaling cascade was affected by all three chemicals. DHT down-regulated the WNT-Frizzled pathway while LIN down-regulated angiopoietin receptor signaling and increased biosynthesis of cholesterol. LIN shared 27 expression sub-networks (e.g. beta-3 adrenergic receptor, MAP3K1, interleukin, signlaing) in common with FLUT, and only 4 sub-networks with DHT. A reciprocal gene expression network was constructed using DHT and FLUT data, and the network revealed that steroid metabolism, translation, and DNA replication are potentially regulated through AR signaling. This study characterizes cell pathways associated with E2 production and identifies cell signaling cascades that may be disrupted by ureic-based herbicides in the ovary. 16 samples total; 4 control, 4 DHT, 4 Flutamide, 4 LIN

2012-07-01 | E-GEOD-38287 | biostudies-arrayexpress

Gene expression profiling in the largemouth bass ovary following sub-chronic dietary exposures to the organochlorine pesticides p,pM-bM-^@M-^Y DDE and methoxychlor

Project description:Largemouth bass (Micropterus salmoides) (LMB) inhabiting Lake Apopka, Florida are exposed to high levels of organochlorine pesticides (OCPs) that exert effects through multiple modes of action. The objectives of this study were to assess the impacts of two OCPs (p,p'-Dichlorodiphenyldichloroethylene; p,pM-bM-^@M-^Y DDE and methoxychlor; MXC) on the reproductive axis of LMB. Female LMB were fed coated feed over 84 days of either 125 (p,pM-bM-^@M-^Y DDE), 10 (MXC), or 0 (control) ppm (mg/kg). In addition, due to the fact that p,pM-bM-^@M-^Y DDE and MXC are suspected anti-androgens, the potent anti-androgenic pharmaceutical flutamide (FLUT) was also fed to a separate group of LMB at 750 ppm. After 84 days, LMB significantly incorporated p,pM-bM-^@M-^Y DDE and MXC into muscle and ovary tissue. Gonadal histology and plasma sex steroids were not significantly different than controls after being fed contaminants. Microarray analysis revealed that p,pM-bM-^@M-^Y DDE and FLUT regulated more genes in common that either chemical compared to MXC, consistent with data suggesting that p,pM-bM-^@M-^Y DDE is a more potent anti-androgen than MXC. There was a significant positive correlation between 71 commonly regulated genes in all three treatments, suggesting that these transcripts may be responding to a common anti-androgenic mode of action. Cell processes affected by all three treatments included leukocyte cell adhesion, ossification, platelet function and inhibition, xenobiotic metabolism, fibrinolysis, and thermoregulation. Most striking was that all three chemicals depressed gene networks related to immune function and inflammation. This study adds to a growing number of fish transcriptomics studies investigating chemicals with an anti-androgenic MOA. 4 biological replicates per group; control, methoxychlor, p,p DDE, and flutamide

2013-08-10 | E-GEOD-47675 | biostudies-arrayexpress

Expression Profiles of HepG2 cells treated with following oxidants: 100µM menadione, 200µM TBH or 50µM H2O2

Project description:The transcriptomic changes induced in the human liver cell line HepG2 by 100µM menadione, 200µM TBH or 50µM H2O2 after treatment for 0.5, 1, 2, 4, 6, 8 and 24h.

2013-05-31 | GSE39291 | GEO

Quantitative proteomic profiling of anti-androgenic sexual endocrine perturbation in zebrafish embryos

Project description:Endocrine disruption (ED) can trigger far-reaching effects on environmental populations, justifying a refusal of market approval for chemicals with ED properties. For the assessment of ED effects on development and reproduction, regulatory decisions mostly rely on apical endpoints from in vivo testing with adult animals. Here, we present a rapid and reproducible data dependent proteomics approach for identifying comprehensive molecular fingerprints interfering with the sexual endocrine system in zebrafish (Danio rerio) embryos as an alternative to animal testing. For this, we have analysed flutamide as model substances for anti-androgenic perturbation in a modified zebrafish embryo toxicity test (zFET). These signatures allow for a definition of solid biomarkers as tools in screening approaches and for integration in chronic toxicity studies for identifying suspect ED substances, in the fish early life-stage test (OECD TG 210).

2023-02-25 | PXD036867 | Pride

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