The effects of environmentally relevant concentrations of aqueous atorvastatin on Xenopus laevis
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PROVIDER: PRJNA989614 | ENA |
REPOSITORIES: ENA
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Project description:Numerous studies report active pharmaceutical compounds detected in both wastewater effluent and surface waters. Exposure to statin drugs in general, and atorvastatin in particular, is likely to be a concern. We hypothesized that chronic exposure to low concentrations of atorvastatin in water would result in an adverse effect on production of steroids regulating growth and development of the model amphibian Xenopus laevis. To assess the potential for impacts we used three experimental assays. The FETAX assay was used to evaluate the effects of a range of doses of atorvastatin on developing embryos. A 60 day metamorphosis assay assessed the effects of aqueous atorvastatin exposure at environmentally concentrations on metamorphosing tadpoles. A 60 day chronic flow-through exposure evaluated the effects of chronic low concentrations of atorvastatin on adults. The data from the FETAX assay confirmed uptake, activity, and effect of atorvastatin in X. laevis tadpoles. The results of the 60-day flow-through exposure on metamorphosing tadpoles showed significant evidence of altered cholesterol biosynthesis. The dose-dependent increase in cyp19a1 expression also indicated that the steroidogenesis pathway was affected. The RNAseq analysis confirmed that exposure to environmentally relevant concentrations of atorvastatin does cause significant alterations to global transcriptional profiles in a manner consistent with dysregulation of the cholesterol biosynthesis pathway, both through the downregulation of many genes involved in that pathway, but also in the impacts to other, related pathways. The qPCR data for both adult males and adult females indicated only slight changes in expression with the exception that hmgcr was significantly downregulated in males, and cyp3a4 expression was significantly downregulated in females. The data we present here indicated that chronic exposure to environmentally relevant concentrations of atorvastatin does have the potential to impact early life stage frogs, particularly by altering expression of genes involved in critical molecular pathways.
2023-07-07 | GSE236279 | GEO
Project description:To investigate the effects of glucocorticoids on the gene expression profiles in zebrafish, we performed a microarray-based transcriptomic study using larvae exposed to three representative glucocoriticoids at environmentally relevant high and low concentrations. Transcriptiomic profiel of developing zebrafish larvae exposed to dexamethasone, prednisolone or triamcinolone at 50 pM to 50 nM from 3 hours post-fertilisation to 5 days post-fertilisation were analyzed using G2519F Agilent Zebrafish Whole Genome Oligo Microarray Ver3.0, 4x44K.
2017-07-01 | GSE93227 | GEO
Project description:Polychlorinated diphenyl ethers are lipophilic, persistent, and bioaccumulable compounds widely used as flame-retardants. These are chemicals of increasing environmental concern due to their lipophilic, persistent, and bioaccumulable characteristics. The objective of this study was to analyze the potential bioavailability and bioaccumulation of BDE-209 as a source of toxicity. Zebrafish embryos were exposed for 8 days to sediments spiked with an environmentally relevant concentration of BDE-209. We analyzed gene expression changes, thyroid function, and several markers for neurotoxicity. Results of this research highlight the need to consider the capability of BDE-209 to be bioavailable and bioaccumulate, indicating the potential hazardous effects.
2013-01-01 | GSE39169 | GEO
Project description:In this study, Lemna minor was used to investigate ecotoxic modes-of-action (MoA) at the gene expression level. For this purpose, mRNA sequencing was applied to plant RNA extracted from L. minor exposed to the pharmaceutical atorvastatin in a shortened version of the OECD guideline test No. 221 (OECD TG 221). L. minor is commonly used as a non-target model organism to determine ecotoxicological effects of xenobiotics. Since atorvastatin (and statins in general) are frequently used pharmaceuticals, they can be found in the aquatic environment. In humans, they are used as cholesterol-lowering agents due to their hydroxymethylglutaryl-CoA reductase (HMGR) inhibitory effect. Analogously, in L. minor, atorvastatin can also inhibit the plant’s HMGR, which is involved in phytosterol synthesis. The aim of our study was to determine a molecular fingerprint of the substance in order to identify potential biomarkers for its MoA. Therefore, we applied bioinformatics approaches to functionally annotate the previously unannotated reference genome of L. minor. Our functional annotation pipeline is in principle applicable to any organism with an available reference genome and thus greatly facilitates the identification of gene functions for poorly annotated organisms. The observed effects at the molecular level showed promising results for the development of OMICs as screening methods as well as for the identification of biomarkers for the toxicity of atorvastatin in L. minor.
2022-07-15 | E-MTAB-11459 | biostudies-arrayexpress
Project description:In the exon array data set, gene level analysis was performed on HepG2 cells exposed to atorvastatin. No genes were found to be statistically significantly differentially expressed upon atorvastatin treatment.
2014-04-26 | GSE57071 | GEO
Project description:The Nation’s streams and rivers contain several contaminants in the form of complex mixtures. These cocktails of chemicals are not equivalent in concentrations, some pollutants such as nutrients can be found in the range of mg/L (macro-pollutants) but others components (micro-pollutants) such as endocrine disrupting chemicals (EDCs) are in amounts thousands to millions of times less concentrated ug/L to ng/L. These mixtures hamper the determination of particular effects of contaminants in aquatic biota. Nonetheless, the fact that toxicity is preceded by alteration in gene expression in an organism allows the use of gene expression profiling (from microarray studies) to detect early toxic effects and identify mechanisms of action. The microarray technology, a collection of DNA fragments attached to a solid surface, can be used to measure the expression levels of large numbers of genes. This facilitates establishment of links between toxicants and effects on biota. In urban waters, micropollutants such as EDCs, are known to cause effects at very low concentrations. One common class of EDCs found in low levels in urban waters is the class of perfluorochemicals (PFCs). Previously, we observed that urban waters with wastewater influence containing PFCs in the 300 ng/L range exerted effects in fish by altering the expression of cholesterol metabolism and DNA repair genes in the liver. To determine whether low concentrations in the range of the PFCs found in the environment can elicit gene expression changes, we investigated the impact of 7 different types of PFCs in a controlled laboratory study by exposing fathead minnows for 48h to environmentally relevant concentrations of PFCs. Additionally, we use blood as starting material for microarray analysis in order to explore non-invasive techniques. No fish mortality was observed in any treatment exposures, but gene expression was altred. Surprisingly, low levels of PFCs that we used altered gene expression in fish liver and blood. Several of the same genes were altered in both liver and blood from exposed fish. Micorarray analysis yields information on altered molecular pathways that predict changes at higher levels of biological organization such as survival and reproduction.
2014-01-30 | GSE54506 | GEO
Project description:Rationale: Immortalized cells may exhibit important differences relative to their primary cell counterparts. Microarrays were used compare primary human umbilical vein endothelial cells (HUVECs) and the immortalized HUVEC cell line EA.hy926, in their response to inhibition of the mevalonate pathway by a HMG-CoA reductase inhibitor (atorvastatin). The effects of atorvastatin were reversed by the addition of mevalonate, to subtract non-specific changes in gene expression. Methods: Confluent cell cultures of HUVECs and EA.hy926 cells (two independent experiments in each cell type) were incubated with 1) statin-free media; 2) 10 microM atorvastatin; 3) 500 microM mevalonate; or 4) a combination of 10 microM atorvastatin and 500 microM mevalonate. All cells were harvested at 24 h. Total RNA was isolated using Trizol reagent (Invitrogen). cDNA was prepared from 10 microgram total RNA using a double-stranded cDNA synthesis kit (Life Technologies) with a T7-dT24 primer for first-strand synthesis. cRNA was synthesized from cDNA and biotinylated using the BioArray High Yield RNA Transcript Labeling Kit (Enzo Diagnostics). Twenty microgram of cRNA was fragmented by heating at 94°C for 35 min in fragmentation buffer, containing 40 mM Tris-acetate, pH 8.1, 125 mM KOAc, 30 mM MgOAc. Fifteen micrgram of fragmented cRNA, together with control cRNAs and grid alignment oligonucleotides, were hybridized overnight to GeneChip Human Genome U133A 2.0 arrays (Affymetrix) at 45°C under constant rotation. Arrays were washed and incubated with an anti-streptavidin antibody. Fluorescent signals were measured using an Agilent Gene Array Laser Scanner and analyzed with MicroArray Suite 5.0 (Affymetrix). Microarrays were scaled using default settings. Keywords: other
2005-03-29 | GSE2450 | GEO
Project description:Xenopus laevis laevis Transcriptome or Gene expression
| PRJNA247381 | ENA
Project description:Aims: Atorvastatin is a commonly used cholesterol-lowering drug that possesses non-canonical anti-inflammatory properties. However, the precise mechanism underlying its anti-inflammatory effects remains unclear. Materials and methods: The acute phase of ulcerative colitis (UC) was induced using a 5 % dextran sulfate sodium (DSS) solution for 7 consecutive days and administrated with atorvastatin (10 mg/kg) from day 3 to day 7. mRNA-seq, histological pathology, and inflammatory response were determined. Intestinal microbiota alteration, tryptophan, and its metabolites were analyzed through 16S rRNA sequencing and untargeted metabolomics. Key findings: Atorvastatin relieved the DSS-induced UC in mice, as evidenced by colon length, body weight, disease activity index score and pathological staining. Atorvastatin treatment reduced the level of pro_x0002_inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Atorvastatin also relieved the intestinal microbiota disorder caused by UC and decreased the proliferation of pernicious microbiota such as Akkermansia and Bacteroides. Atorvastatin dramatically altered tryptophan metabolism and increased the fecal contents of tryptophan, indolelactic acid (ILA), and indole-3-acetic acid (IAA). Furthermore, atorvastatin enhanced the expression level of aryl hydrocarbon receptor (AhR) and interleukin-22 (IL-22) and further promoted the expression level of intestinal tight junction proteins, such as ZO-1 and occludin, in colitis mice. Significance: These findings indicated that atorvastatin could alleviate UC by regulating intestinal flora disorders, promoting microbial tryptophan metabolism, and repairing the intestinal barrier.
2024-11-04 | GSE280960 | GEO
Project description:In the exon array data set, gene level analysis was performed on HepG2 cells exposed to atorvastatin. No genes were found to be statistically significantly differentially expressed upon atorvastatin treatment. 3 control and 3 atorvastatin treated HepG2 samples were analysed. Genes with an FDRM-bM-^IM-$5% after Benjamini-Hochberg correction was considered as differentially expressed.
2014-04-26 | E-GEOD-57071 | biostudies-arrayexpress