Alteration of lipid homeostasis by hydroxypropyl cyclodextrin improves amiodarone-induced alveolar cell disorder
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE146612 | GEO | 2021/02/20
REPOSITORIES: GEO
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Project description:Alteration of lipid homeostasis by hydroxypropyl cyclodextrin improves amiodarone-induced alveolar cell disorder
| PRJNA611495 | ENA
Project description:Amiodarone reversibly decreases sodium-iodide symporter mRNA expression at therapeutic concentrations and induces antioxidant responses at supraphysiological concentrations in cultured human thyroid follicles Amiodarone, a potent antiarrhythmic agent, is a highly active oxidant, exerting cytotoxic effects on thyrocytes at pharmacological concentrations. Patients receiving amiodarone usually remain euthyroid, but occasionally develop thyroid dysfunction, such as amiodarone-associated hypothyroidism or amiodarone-induced thyrotoxicosis. To elucidate the mechanism by which amiodarone elicits thyroid dysfunction, human thyroid follicles were cultured with TSH and amiodarone at therapeutic (1-2 microM) and pharmacological (10-20microM) concentrations, and the drug-induced effect on whole human gene expression was analyzed by cDNA microarray. Amiodarone at 1-2microM decreased the expression level of the sodium-iodide symporter (NIS) to nearly half, but did not affect genes participating in thyroid hormonogenesis (thyroid peroxidase, thyroglobulin, pendrin, NADPH oxidase). Higher concentrations (10-20 microM) decreased the expression of all these genes, accompanied by increased expression of antioxidant proteins such as heme oxygenase 1 and ferritin. When thyroid follicles obtained from a patient with Graves’ disease who had been treated with amiodarone for 2 months before thyroidectomy were cultured in amiodarone-free medium, TSH-induced thyroid function was intact, suggesting that amiodarone at a maintenance dose did not elicit any cytotoxic effect on thyrocytes. The ultrastructural features of cultured thyroid follicles were compatible with these in vitro findings. These in vitro and ex vivo findings suggest that patients taking maintenance doses of amiodarone usually remain euthyroid, probably due to escape from the Wolff-Chaikoff effect mediated by decreased expression of NIS mRNA. Furthermore, amiodarone is not cytotoxic for thyrocytes at therapeutic concentrations but elicits cytotoxicity through oxidant activity at supra-physiological concentrations. Keywords: Cultured human thyroid follicles
2008-07-19 | GSE12164 | GEO
Project description:AAmiodarone is an antiarrhythmic drug and representatively induce pulmonary phospholipidosis. Amiodarone-induced toxicity has been a serious unpredictable side effect of the treatment and an important clinical problem. Possible causes include allergic, cytotoxic or immunologic reactions to this agent. We examined the consequences of the mechanism of amiodarone-induced pulmonary toxicity gene expression in BEAS-2B cells, huma bronchial cell line, by microarray. The expression of these genes are potential biomarker of amiodarone-induced pulmonary toxicity. Also, We provide a clue about mechanism of pulmonary toxic action by these clinical chemotherapeutic agents.
2011-01-10 | GSE20582 | GEO
Project description:To verify the acetylation effect of amiodarone on HL-60 cells, we treated HL-60 cells with 10 渭M amiodarone for 24 h and collected cells for acetylation protein detection
2024-01-16 | PXD048570 | Pride
Project description:Interstitial lung disease (ILD) is a group of respiratory disorders characterized by chronic inflammation and fibrosis of the pulmonary interstitial tissues. Although the etiology of ILD remains unclear, some drug treatments are one of the primary causes of ILD. In the present study, we analyzed FDA Adverse Event Reporting System and JMDC insurance claims to find a coexisting drug that reduced the incidence of ILD associated with use of an anti-arrhythmic agent, amiodarone, and found that the thrombin inhibitor dabigatran prevented the amiodarone-induced ILD in both clinical datasets. In an experimental validation of the hypothesis, a long-term, oral treatment of mice with amiodarone caused a gradual decrease in the body weight caused by respiratory insufficiency. In the lung of amiodarone-treated mice, infiltration of macrophages and interstitial thickening were observed in parallel with a delayed upregulation of platelet-derived growth factor receptor α gene. In contrast, co-treatment with dabigatran significantly attenuated these amiodarone-induced changes representing ILD. These results suggest that dabigatran is effective in preventing the drug-induced ILD. This combinatorial approach of drug repositioning based on clinical big data will pave the way for finding a new treatment with high clinical predictability and a well-defined molecular mechanism.
2020-12-03 | GSE162229 | GEO
Project description:AAmiodarone is an antiarrhythmic drug and representatively induce pulmonary phospholipidosis. Amiodarone-induced toxicity has been a serious unpredictable side effect of the treatment and an important clinical problem. Possible causes include allergic, cytotoxic or immunologic reactions to this agent. We examined the consequences of the mechanism of amiodarone-induced pulmonary toxicity gene expression in BEAS-2B cells, huma bronchial cell line, by microarray. The expression of these genes are potential biomarker of amiodarone-induced pulmonary toxicity. Also, We provide a clue about mechanism of pulmonary toxic action by these clinical chemotherapeutic agents. BEAS-2B cells were seeded and after incubation for 24 h at 37C, the cells were treated with 29.388 μM(IC20) amiodarone for 48 h. And after total RNA isolation, gene expression analysis was conducted using a 44-k whole human genome microarray. Labeling and hybridization were performed using a FairPlay microarray labeling kit, followed by the coupling of Cy3 (controls) or Cy5 (treated samples) dye. The hybridized slides were scanned using a GenePix 4000B microarray scanner, and the images were analyzed using GenePix 4.1 software to obtain gene expression ratios. The fluorescence intensity of each spot was calculated by local median background subtraction. We then used the robust scatter-plot smoother LOWESS function to perform intensity-dependent normalization of gene expression. Scatter-plot analysis was performed using Microsoft Excel 2000. A significance analysis of microarray (SAM) was performed for genes with significant changes in expression.
2011-01-10 | E-GEOD-20582 | biostudies-arrayexpress
Project description:In experiments using tissue recombinants and mesenchyme-free culture, we have demonstrated that the entire embryonic respiratory tract epithelium, from the trachea to the distal lung tips, exhibits substantial plasticity in its eventual phenotype that is dependent on the inductive cues it receives from its associated mesenchyme. This observation led us to speculate that the differences between embryonic trachea and lung are defined by limited subset of genes, and that the molecular comparison of these two tissues might provide new information on genes that are important for both lung and trachea development. Microarray experiments designed to identify genes differentially expressed in the E11.5 lung and trachea showed that melanoma inhibitory activity (Mia1) was expressed only in the lung. Mia1 was abundantly expressed during early lung development, but was virtually absent by the end of gestation. Bitransgenic mice expressing MIA under the control of the SFTPC promoter after E16.5, the age when Mia1 is normally silenced, died from respiratory failure at birth with morphologically immature lungs associated with reduced levels of saturated phosphatidylcholine and mature SP-B. Microarray analysis showed significant reductions expression of Sftpa, Sftpb, Abca3, Aqp5, Lzp-s, Scd2, and Aytl2 in lungs misexpressing MIA. Experiment Overall Design: To identify genes differentially expressed in the embryonic lung and trachea, we used microarray analysis to compare RNA from day E11.5 mouse lung and trachea. Experiment Overall Design: To assess the effect of misexpressing MIA on overall lung gene expression, we analyzed RNA from day E18.5 lungs of bitransgenic and control littermates by microarray (Affymetrix MOE430 chip).
2008-06-16 | E-GEOD-9312 | biostudies-arrayexpress
Project description:In the present study, an oligonucleotide microarray platform was used to compare expression profiles of heart and blood in rats treated with amiodarone against respective controls. Male Sprague-Dawley (CD) rats, which were 10 weeks old and weighed 290-320 grams at the beginning of the study, have been treated for ten days with amiodarone by oral route at a dose of 300mg/Kg/die. The study has been constituted by a control group, which received the vehicle (methylcellulose 1%, w/v), and by a treatment group (10 animals for both groups). For each tissue sample, total RNA has been individually extracted and evaluated. For each tissue, three pools/group (2 pools composed of 3 animals and the last one by 4) have been used for microarray analysis. A modulation of 600 genes in heart and 8300 genes in blood has been obtained.
2015-03-23 | GSE24213 | GEO
Project description:We performed transcriptomic profiling of patient induced pluripotent stem cell (iPSC)-derived iAEC2s containing E690K and W308R ABCA3 mutations as well as their syngeneic, gene-corrected iAEC2s (total of four iPSC-derived iAEC2 lines). We first reprogrammed iPSCs from 2 patients with two homozyguos ABCA3 mutations (E690K and W308R ABCA3 mutations). Next we utilized TALENs gene-editing technique previously published in Jacob et al. (2017) to monoallelically target the endogenous SFTPC locus with the tdTomato reporter, allowing for sorting and isolation of SFTPCtdTomato positive iAEC2s. Finally, we used CRISPR-Cas9 footprint-free gene-correction to generate syngeneic patient iPSCs which were dfferentiated into the corresponding iAEC2s for syngeneic comparisons. Following tripplicate differentiations of all 4 patient iPSC lines, we sorted the SFTPCtdTomato+ iAEC2s on day 43-44 of differentiation for transcriptomic analyses.
2023-06-01 | GSE205318 | GEO
Project description:We made a RNAseq in HL-60 cells to measure the changes in global transcript levels in HL-60 cells after amiodarone treatment.
2024-01-18 | GSE253113 | GEO