Flutamide treated rat hepatocytes in microfluidic biochips
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE44317 | GEO | 2013/12/01
SECONDARY ACCESSION(S): PRJNA189450
REPOSITORIES: GEO
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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
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.
2014-03-06 | GSE44263 | GEO
Project description:Flutamide treated rat hepatocytes in microfluidic biochips
| PRJNA189450 | ENA
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
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
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
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
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
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
Project description:BACKGROUND & AIMS: c-Jun N-terminal kinase (JNK)1 and JNK2 are expressed in hepatocytes and have overlapping and distinct functions. JNK proteins are activated, via phosphorylation, in response to acetaminophen- or CCl4-induced liver damage; the level of activation correlates with the degree of injury. SP600125, a JNK inhibitor, has been reported to block acetaminophen-induced liver injury. We investigated the role of JNK in drug-induced liver injury (DILI) in liver tissues from patients and in mice with genetic deletion of JNK in hepatocytes. METHODS: We studied liver sections from patients with DILI (due to acetaminophen, phenprocoumon, non-steroidal anti-inflammatory drugs or autoimmune hepatitis), or patients without acute liver failure (controls), collected from a DILI Biobank in Germany. Levels of total and activated (phosphorylated) JNK were measured by immunohistochemistry and western blotting. Mice with hepatocyte-specific deletion of Jnk1 (Jnk1Îhepa) or combination of Jnk1 and Jnk2 (JnkÎhepa), as well as Jnk1-floxed C57BL/6 (control) mice, were given injections of CCl4 (to induce fibrosis) or acetaminophen (to induce toxic liver injury). We performed gene expression microarray, and phosphoproteomic analyses to determine mechanisms of JNK activity in hepatocytes. RESULTS: Liver samples from DILI patients contained more activated JNK, predominantly in nuclei of hepatocytes and in immune cells, than healthy tissue. Administration of acetaminophen to JnkÎhepa mice produced a greater level of liver injury than that observed in Jnk1Îhepa or control mice, based on levels of serum markers and microscopic and histologic analysis of liver tissues. Administration of CCl4 also induced stronger hepatic injury in JnkÎhepa mice, based on increased inflammation, cell proliferation, and fibrosis progression, compared to Jnk1Îhepa or control mice. Hepatocytes from JnkÎhepa mice given acetaminophen had an increased oxidative stress response, leading to decreased activation of AMPK, total protein AMPK levels, and pJunD and subsequent necrosis. Administration of SP600125 before or with acetaminophen protected JnkÎhepa and control mice from liver injury. CONCLUSIONS: In hepatocytes, JNK1 and JNK2 appear to have combined effects in protecting mice from CCl4- and acetaminophen-induced liver injury. It is important to study the tissue-specific functions of both proteins, rather than just JNK1, in the onset of toxic liver injury. JNK inhibition with SP600125 shows off-target effects. Livers and primary hepatocytes were isolated from wild type and JNKÎhepa (Jnk1Îhepa/global Jnk2-/-) double-knockout mice and subjected to gene expression profiling.
2016-01-04 | E-GEOD-59602 | biostudies-arrayexpress