Triphenyl Phosphate Alters Methyltransferase Expression and Induces Genome-Wide Aberrant DNA Methylation in Zebrafish Larvae DOI Creative Commons
Chander K. Negi,

Lucie Bláhová,

Audrey Phan

et al.

Chemical Research in Toxicology, Journal Year: 2024, Volume and Issue: 37(9), P. 1549 - 1561

Published: Aug. 29, 2024

Emerging environmental contaminants, organophosphate flame retardants (OPFRs), pose significant threats to ecosystems and human health. Despite numerous studies reporting the toxic effects of OPFRs, research on their epigenetic alterations remains limited. In this study, we investigated exposure 2-ethylhexyl diphenyl phosphate (EHDPP), tricresyl (TMPP), triphenyl (TPHP) DNA methylation patterns during zebrafish embryonic development. We assessed general toxicity morphological changes, measured global hydroxymethylation levels, evaluated methyltransferase (DNMT) enzyme activity, as well mRNA expression DNMTs ten-eleven translocation (TET) methylcytosine dioxygenase genes. Additionally, analyzed genome-wide in larvae using reduced-representation bisulfite sequencing. Our assessment revealed no toxicity, but a statistically yet subtle decrease body length following TMPP EHDPP, along with reduction head height after TPHP exposure, was observed. Eye diameter width were unaffected by any OPFRs. There changes levels group, showed clear effect DNMT expression. However, EHDPP significantly decreased only DNMT1 expression, while reduced several orthologues TETs larvae, leading aberrant methylation. Differential occurred primarily introns (43%) intergenic regions (37%), 9% 10% occurring exons promoter regions, respectively. Pathway enrichment analysis differentially methylated region-associated genes indicated that enhanced biological molecular functions corresponding metabolism neurological KEGG further TPHP-mediated potential signaling pathways including TGFβ, cytokine, insulin signaling. This study identifies specific brings novel insights into mode action TPHP.

Language: Английский

Cellular and physiological mechanisms of halogenated and organophosphorus flame retardant toxicity DOI Creative Commons
Leila Khani, Leonardo Martín, Łukasz Pułaski

et al.

The Science of The Total Environment, Journal Year: 2023, Volume and Issue: 897, P. 165272 - 165272

Published: July 3, 2023

Flame retardants (FRs) are chemical substances used to inhibit the spread of fire in numerous industrial applications, and their abundance modern manufactured products indoor outdoor environment leads extensive direct food chain exposure humans. Although once considered relatively non-toxic, FRs demonstrated by recent literature have disruptive effects on many biological processes, including signaling pathways, genome stability, reproduction, immune system function. This review provides a summary research investigating impact major groups FRs, halogenated organophosphorus animals humans vitro and/or vivo. We put focus those studies that explained or referenced modes FR action at level cells, tissues organs. Since highly hydrophobic chemicals, biophysical biochemical usually involve lipophilic interactions, e.g. with membranes elements pathways. present selected toxicological information about these molecular actions show how they can lead damaging membrane integrity, DNA compromising its repair, changing gene expression, cell cycle as well accelerating death. Moreover, we indicate this translates deleterious bioactivity physiological level, disruption hormonal action, dysregulation metabolism, adverse male female reproduction alteration normal pattern immunity. Concentrating subjects, make clear both advances knowledge years remaining gaps our understanding, especially mechanistic level.

Language: Английский

Citations

22
Association of co-exposure to organophosphate esters and per- and polyfluoroalkyl substances and mixture with cardiovascular-kidney-liver-metabolic biomarkers among Chinese adults DOI Creative Commons
Yanbing Li,

Yi Lv,

Zexuan Jiang

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 280, P. 116524 - 116524

Published: June 5, 2024

Organophosphate esters (OPEs) and Per- polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants with common exposure sources, leading to their widespread presence in human body. However, evidence on co-exposure OPEs PFAS its impact cardiovascular-kidney-liver-metabolic biomarkers remains limited.

Language: Английский

Citations

8
Biodegradation of aryl-organophosphate flame retardants by Rhodococcus pyridinivorans YC-MTN: Performance, pathway and potential in environmental remediation DOI
Long Yuan, Junhuan Wang,

May Thet Nwe

et al.

International Biodeterioration & Biodegradation, Journal Year: 2024, Volume and Issue: 190, P. 105772 - 105772

Published: March 11, 2024

Language: Английский

Citations

4
Biotransformation, Bioaccumulation, and Bioelimination of Triphenyl Phosphate and Its Dominant Metabolite Diphenyl Phosphate In Vivo DOI

Jing Cao,

Yumeng Lei, Xiaofeng Jiang

et al.

Environmental Science & Technology, Journal Year: 2024, Volume and Issue: 58(35), P. 15486 - 15496

Published: Aug. 21, 2024

Aryl phosphorus flame retardants (aryl-PFRs), such as triphenyl phosphate (TPHP) and diphenyl (DPHP), are widely used worldwide. Understanding the fates of aryl-PFRs

Language: Английский

Citations

4
New insights into the mechanism of triphenyl phosphate and its metabolite diphenyl phosphate in diabetic kidney disease DOI Creative Commons
Ting Fang, Qiaoyan Liu,

Xinxin Huangfu

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 291, P. 117877 - 117877

Published: Feb. 1, 2025

Diabetic kidney disease is a significant complication of diabetes mellitus, and exposure to certain chemicals may play role in its development. Triphenyl phosphate (TPHP) commonly used plastics flame retardants. This study aims investigate the potential impact TPHP metabolite diphenyl (DPHP) on diabetic using various methods, including network toxicology, molecular docking, cell experiments like CCK8 assay real-time-PCR. The research examined relationship between urinary DPHP levels function American adults data from National Health Nutrition Examination Survey (NHANES) 2017 March 2020. Additionally, explored targets action for toxicity analysis, conducted protein interaction functional aspects through Gene Ontology Kyoto Encyclopedia Genes Genomes enrichment analysis. Furthermore, identified key proteins involved experimental verification by treating cells with DPHP. Toxicity analysis showed that could cause dose-dependent mouse podocyte clone 5 (MPC5) mesangial (MES13). also detected mRNA expression core molecularly docked results indicated statistically regulation most MPC5, MES13, human kidney-2 cells.

Language: Английский

Citations

0
Revealing the neurodevelopmental toxicity of face mask-derived microplastics to humans based on neural organoids DOI
Minghui Li, Xue Gao,

Yingying Lan

et al.

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: unknown, P. 138084 - 138084

Published: March 1, 2025

Language: Английский

Citations

0
Health Risks of Low-Dose Dietary Exposure to Triphenyl Phosphate and Diphenyl Phosphate in Mice: Insights from the Gut–Liver Axis DOI

Jing Cao,

Xinwei Wang, Yumeng Lei

et al.

Environmental Science & Technology, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

Aryl phosphate esters have been detected throughout the natural environment and in human blood samples, making it important to determine health risks associated with exposure triphenyl (TPHP) its metabolite diphenyl (DPHP). Here, C57BL/6J male mice were exposed TPHP or DPHP for 12 weeks at estimated daily intake doses of 0.1 7 μg/kg bw/day. affected levels short-chain fatty acids bile gut, enhancing production 29 medium- long-chain liver by 3.72-fold significantly increasing hepatic lipid cholesterol levels. Metabolomic molecular analysis confirmed that elevated persisted after an 8 week recovery period. Gut microbiota-dependent alterations toxic end points observed TPHP-fed mice, as supported results fecal microbiota transplantation. In DPHP-fed serotonergic glutamatergic synapses simultaneously altered intestine, corresponding reduction five brain neurotransmitters (15.4-60.8%). Decreased carbohydrate insulin resistance mice. These suggest affect metabolism via different modes, mediated through gut-liver axis, providing novel insights into mechanisms organophosphate-ester-mediated metabolic disruption.

Language: Английский

Citations

0
Triphenyl phosphate‐induced macrophages dysfunction by activation TLR4‐mediated ERK/NF‐κB pathway DOI

Zeheng Lin,

Wei Zhang, Xing Li

et al.

Environmental Toxicology, Journal Year: 2023, Volume and Issue: 38(7), P. 1484 - 1493

Published: March 17, 2023

Abstract Triphenyl phosphate (TPHP) is one of the most widely used organic phosphorus flame retardants and ubiquitous in environment. Studies have been reported that TPHP may lead to obesity, neurotoxicity reproductive toxicity, but its impact on immune system almost blank. The present study was aimed investigate potential immunotoxicity macrophages underlying mechanism. results demonstrated for first time (12.5, 25, 50 μM)‐induced F4/80 + CD11c phenotype RAW 264.7 macrophages, accompanied by increased mRNA levels inflammatory mediators, antigen‐presenting genes (Cd80, Cd86, H2‐Aa), significantly enhanced phagocytosis macrophage. Meanwhile, expression Toll‐like receptor 4 (TLR4), co‐receptor CD14, leading significant activation downstream ERK/NF‐κB pathway. However, co‐exposure cells TAK‐242, a TLR4 inhibitor, suppressed TPHP‐induced phenotype, down‐regulated mediators antigen‐presentation related genes, via blocked TLR4/ERK/NF‐κB Taken together, our suggested could induce macrophage dysfunction through activating TLR4‐mediated signaling pathway, it be reason health‐threatening consequences.

Language: Английский

Citations

9
The flame retardant triphenyl phosphate alters the epigenome of embryonic cells in an aquatic in vitro model DOI Creative Commons

Logan Germain,

Louise M. Winn

Journal of Applied Toxicology, Journal Year: 2024, Volume and Issue: 44(7), P. 965 - 977

Published: Feb. 28, 2024

Abstract Triphenyl phosphate (TPhP) is an organophosphate flame retardant and plasticizer that added to a wide variety of consumer industrial products. It also ubiquitous environmental pollutant. Exposure TPhP has been shown alter gene expression in metabolic estrogenic signaling pathways vitro vivo models species, as such, considered be endocrine disrupting chemical. chemicals increasingly being associated with changes the epigenome, especially during embryonic development. The aim this study was evaluate whether exposure aquatic ecosystems ability epigenome two immortal cell lines derived from trout ( Oncorhynchus mykiss ). This assessed 24 h resulted histone modification DNA methylation profiles steelhead cells rainbow gill epithelial cells. Results show several epigenetic modifications on H3 are altered following exposure, but not Specifically, acetylation, mono‐methylation global were found reduced. alterations these suggest fetal development may developing embryo, likely pathways. impacts determined even carry multigenerational detrimental effects human ecosystem health, which requires further investigation.

Language: Английский

Citations

3
The investigation of the toxicity of organophosphorus flame retardants (OPFRs) by using in silico toxicity prediction platform ProTox- 3.0 DOI
Priyanka Banerjee, Onur Ülker, Irem Ozkan

et al.

Toxicology Mechanisms and Methods, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 11

Published: July 25, 2024

From the past to present, many chemicals have been used for purpose of flame retardant. Due PBDEs' (Polybrominated diphenyl ether) lipophilic and accumulative properties, some them are banned from market. As an alternative these chemicals, OPFRs (organophosphorus retardants) started be as retardants. In this article, acute toxicity profiles, mutagenicity, carcinogenicity, blood-brain barrier permeability, ecotoxicity nutritional also AHR, ER affinity MMP, aromatase affinity, CYP2C9, CYP3A4 interaction 16 different compounds were investigated using a computational toxicology method; ProTox- 3.0. According our results, eight found active in terms carcinogenic effect, whereas two mutagenicity. On other hand, all blood-barrier permeability. Fourteen four ecotoxic toxic potency, respectively. Eight determined AhR, Estrogen Receptor alpha. mitochondrial membrane potency. Lastly, three enzymes. CYP potencies, both CYP2C9 CYP3A4. This research provided novel insights into potential effects OPFRs. However, further studies needed evaluate their toxicity. Moreover, findings lay groundwork

Language: Английский

Citations

3