scholarly journals Investigation on Sex Hormone-Disruption Effects of Two Novel Brominated Flame Retardants (DBDPE and BTBPE) in Male Zebrafish (Danio rerio) and Two Human Cell Lines (H295R and MVLN)

2021 ◽  
Vol 11 (9) ◽  
pp. 3837
Author(s):  
Jiwon Choi ◽  
Gowoon Lee ◽  
Sunmi Kim ◽  
Kyungho Choi
Keyword(s):  
Cell Lines ◽  
Danio Rerio ◽  
Flame Retardants ◽  
Experimental Studies ◽  
Brominated Flame Retardants ◽  
Sex Hormone ◽  
Hormone Regulation ◽  
Increasing Trend ◽  
H295r Cells

Decabromodiphenyl ethane (DBDPE) and 1,2-bis(2,4,6-tribromo-phenoxy) ethane (BTBPE) are novel brominated flame retardants (NBFRs) and have been detected in variety of environment and biota. Although sex endocrine-disrupting potential has been suggested in experimental studies, their adverse effects on sex steroid hormones and underlying mechanisms are largely unclear. The purpose of the present study is to investigate the sex hormone-disrupting effects of two NBFRs using in vivo and in vitro models together. For this, male zebrafish (Danio rerio) along with human adrenocortical carcinoma (H295R) and breast carcinoma (MVLN) cell lines were employed. In male zebrafish, 14-day exposure to DBDPE significantly increased 17β-estradiol (E2) concentrations. Disruption of sex hormone regulation was also suggested after exposure to BTBPE, i.e., the increasing trend of E2 levels, E2/11-ketotestosterone (11-KT) ratio, and estrogen receptor-alpha (erα) and erβ gene expression levels. In H295R cells, an E2/T ratio showed an increasing trend by DBDPE exposure, but transcriptions of major genes in steroidogenesis pathway were not affected. Taken together, our observation implies that two NBFRs could cause the sex hormone disruption potential in male zebrafish and H295R cells but probably not through alteration of steroidogenesis pathway.

scholarly journals Transcriptomic Analysis of the Differential Nephrotoxicity of Diverse Brominated Flame Retardants in Rat and Human Renal Cells

2021 ◽  
Vol 22 (18) ◽  
pp. 10044
Author(s):  
Lillie Marie A. Barnett ◽  
Naomi E. Kramer ◽  
Amanda N. Buerger ◽  
Deirdre H. Love ◽  
Joseph H. Bisesi ◽  
...  
Keyword(s):  
Cell Lines ◽  
Flame Retardants ◽  
Molecular Mechanisms ◽  
Annexin V ◽  
Enrichment Analysis ◽  
Brominated Flame Retardants ◽  
Human Cells ◽  
Gene Set Enrichment Analysis ◽  
Coagulation Cascade ◽  
Transcriptional Changes

Brominated flame retardants (BFRs) are environmentally persistent, are detected in humans, and some have been banned due to their potential toxicity. BFRs are developmental neurotoxicants and endocrine disruptors; however, few studies have explored their potential nephrotoxicity. We addressed this gap in the literature by determining the toxicity of three different BFRs (tetrabromobisphenol A (TBBPA), hexabromocyclododecane (HBCD), and tetrabromodiphenyl ether (BDE-47)) in rat (NRK 52E) and human (HK-2 and RPTEC) tubular epithelial cells. All compounds induced time- and concentration-dependent toxicity based on decreases in MTT staining and changes in cell and nuclear morphology. The toxicity of BFRs was chemical- and cell-dependent, and human cells were more susceptible to all three BFRs based on IC50s after 48 h exposure. BFRs also had chemical- and cell-dependent effects on apoptosis as measured by increases in annexin V and PI staining. The molecular mechanisms mediating this toxicity were investigated using RNA sequencing. Principal components analysis supported the hypothesis that BFRs induce different transcriptional changes in rat and human cells. Furthermore, BFRs only shared nine differentially expressed genes in rat cells and five in human cells. Gene set enrichment analysis demonstrated chemical- and cell-dependent effects; however, some commonalities were also observed. Namely, gene sets associated with extracellular matrix turnover, the coagulation cascade, and the SNS-related adrenal cortex response were enriched across all cell lines and BFR treatments. Taken together, these data support the hypothesis that BFRs induce differential toxicity in rat and human renal cell lines that is mediated by differential changes in gene expression.

scholarly journals Development of an oxidative stress in vitro assay in zebrafish (Danio rerio) cell lines

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Sebastian Lungu-Mitea ◽  
Agneta Oskarsson ◽  
Johan Lundqvist
Keyword(s):  
Oxidative Stress ◽  
Cell Lines ◽  
Danio Rerio ◽  
In Vitro Assay ◽  
Vitro Assay

Maternal transfer of brominated flame retardants in zebrafish (Danio rerio)

Chemosphere ◽  
2008 ◽  
Vol 73 (2) ◽  
pp. 203-208 ◽  
Author(s):  
Jenny Rattfelt Nyholm ◽  
Anna Norman ◽  
Leif Norrgren ◽  
Peter Haglund ◽  
Patrik L. Andersson
Keyword(s):  
Danio Rerio ◽  
Flame Retardants ◽  
Brominated Flame Retardants ◽  
Maternal Transfer

scholarly journals Integrated Bioinformatics Data Analysis and Experimental Studies Reveals Prognostic Significance of ALDH Family in Endometria Cancer

2021 ◽  
Author(s):  
Zhou-Tong Dai ◽  
Yuan Xiang ◽  
Xing-Hua Liao
Keyword(s):  
Cell Lines ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Experimental Studies ◽  
Female Reproductive Tract ◽  
The Body ◽  
Mouse Tumor ◽  
The Impact

Abstract Background Uterine Corpus Endometrial Cancer (UCEC) is one of the three common malignant tumors of the female reproductive tract. According to reports, the cure rate of early UCEC can reach 95%. Therefore, the development of prognostic markers will help UCEC patients to find the disease earlier and develop treatment earlier. The ALDH family was first discovered to be the essential gene of the ethanol metabolism pathway in the body. Recent studies have shown that ALDH can participate in the regulation of cancer. Methods We used the gene profile data of 33 cancers in the TCGA database to analyze the expression and survival of the ALDH family. GO, KEGG, PPI multiple functional analysis was used to predict the regulatory role of ALDH family in cancer. In addition, using CCK-8, colony formation, nude mouse tumor formation and other methods, the in vitro function of UCEC cancer cell lines was tested to further confirm the key role of ALDH2 expression in the proliferation of UCEC cell lines. Finally, Lasso and Cox regression methods were used to establish an overall survival prognosis model based on ALDH2 expression. Result In our research, we explored the expression of ALDH family in 33 cancers. It was found that ALDH2 was abnormally expressed in UCEC. Besides, in vivo and in vitro experiments were conducted to explore the effect of ALDH2 expression on the proliferation of UCEC cell lines. Meanwhile, the change of its expression is not due to gene mutations, but is regulated by miR-135-3p. At the same time, the impact of ALDH2 changes on the survival of UCEC patients is deeply discussed. Finally, a nomogram for predicting survival was constructed, with a C-index of 0.798 and AUC of 0.764. Conclusion This study suggests that ALDH2 may play a crucial role in UCEC progression and has the potential as a prognostic biomarker of UCEC.

Acute in vitro Nephrotoxicity of Three Brominated Flame Retardants

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Lillie Barnett ◽  
Brian S. Cummings
Keyword(s):  
Flame Retardants ◽  
Brominated Flame Retardants

Impact of brominated flame retardants on lipid metabolism: An in vitro approach

2022 ◽  
Vol 294 ◽  
pp. 118639
Author(s):  
Maria Luz Maia ◽  
Sara Sousa ◽  
Diogo Pestana ◽  
Ana Faria ◽  
Diana Teixeira ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Flame Retardants ◽  
Brominated Flame Retardants

scholarly journals Fluconazole inhibits human adrenocortical steroidogenesis in vitro

2012 ◽  
Vol 215 (3) ◽  
pp. 403-412 ◽  
Author(s):  
R van der Pas ◽  
L J Hofland ◽  
J Hofland ◽  
A E Taylor ◽  
W Arlt ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Cell Lines ◽  
Primary Cultures ◽  
Cell Number ◽  
Mrna Levels ◽  
Steroidogenic Enzymes ◽  
Maximum Inhibition ◽  
H295r Cells ◽  
17 Hydroxyprogesterone

The antifungal agent ketoconazole is often used to suppress cortisol production in patients with Cushing's syndrome (CS). However, ketoconazole has serious side effects and is hepatotoxic. Here, the in vitro effects of ketoconazole and fluconazole, which might be less toxic, on human adrenocortical steroidogenesis were compared. The effects on steroidogenesis were examined in primary cultures of nine human adrenocortical tissues and two human adrenocortical carcinoma cell lines. Moreover, the effects on mRNA expression levels of steroidogenic enzymes and cell growth were assessed. Ketoconazole significantly inhibited 11-deoxycortisol (H295R cells; maximum inhibition 99%; EC50 0.73 μM) and cortisol production (HAC15 cells; 81%; EC50 0.26 μM and primary cultures (mean EC50 0.75 μM)). In cultures of normal adrenal cells, ketoconazole increased pregnenolone, progesterone, and deoxycorticosterone levels, while concentrations of 17-hydroxypregnenolone, 17-hydroxyprogesterone, 11-deoxycortisol, DHEA, and androstenedione decreased. Fluconazole also inhibited 11-deoxycortisol production in H295R cells (47%; only at 1 mM) and cortisol production in HAC15 cells (maximum inhibition 55%; EC50 35 μM) and primary cultures (mean EC50 67.7 μM). In the cultures of normal adrenals, fluconazole suppressed corticosterone, 17-hydroxypregnenolone, and androstenedione levels, whereas concentrations of progesterone, deoxycorticosterone, and 11-deoxycortisol increased. Fluconazole (1 mM) slightly increased STAR mRNA expression in both cell lines. Neither compound affected mRNA levels of other steroidogenic enzymes or cell number. In conclusion, by inhibiting 11β-hydroxylase and 17-hydroxylase activity, pharmacological concentrations of fluconazole dose dependently inhibit cortisol production in human adrenocortical cells in vitro. Although fluconazole seems less potent than ketoconazole, it might become an alternative for ketoconazole to control hypercortisolism in CS. Furthermore, patients receiving fluconazole because of mycosis might be at risk for developing adrenocortical insufficiency.

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