Cellular and physiological mechanisms of halogenated and organophosphorus flame retardant toxicity

The Science of The Total Environment, Год журнала: 2023, Номер 897, С. 165272 - 165272

Опубликована: Июль 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.

Язык: Английский

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Association of co-exposure to organophosphate esters and per- and polyfluoroalkyl substances and mixture with cardiovascular-kidney-liver-metabolic biomarkers among Chinese adults

Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 280, С. 116524 - 116524

Опубликована: Июнь 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.

Язык: Английский

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Biodegradation of aryl-organophosphate flame retardants by Rhodococcus pyridinivorans YC-MTN: Performance, pathway and potential in environmental remediation

International Biodeterioration & Biodegradation, Год журнала: 2024, Номер 190, С. 105772 - 105772

Опубликована: Март 11, 2024

Язык: Английский

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Mild endoplasmic reticulum stress alleviates FB1-triggered intestinal pyroptosis via the Sec62-PERK pathway

Cell Biology and Toxicology, Год журнала: 2024, Номер 40(1)

Опубликована: Май 21, 2024

Fumonisin B1 (FB1), a water-soluble mycotoxin released by Fusarium moniliforme Sheld, is widely present in corn and its derivative products, seriously endangers human life health. Recent studies have reported that FB1 can lead to pyroptosis, however, the mechanisms which FB1-induced pyroptosis remain indistinct. In study, we aim investigate of intestinal porcine epithelial cells (IPEC-J2) relationship between endoplasmic reticulum stress (ERS) pyroptosis. Our experimental results showed protein indicators IPEC-J2 were significantly increased after exposure FB1. The ERS markers, including glucose-regulated Protein 78 (GRP78), PKR-like ER kinase (PERK), preprotein translocation factor (Sec62) also increased. Using small interfering RNA silencing PERK or Sec62, demonstrated upregulation Sec62 activates pathway, activation signaling pathway upstream After using inhibitor 4-PBA reduced FB1-triggered injury Sec62-PERK pathway. conclusion, found induced upregulating activate mild alleviates damage. It all boils down one fact, study provides new perspective for further, improving toxicological mechanism

Язык: Английский

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The investigation of the toxicity of organophosphorus flame retardants (OPFRs) by using in silico toxicity prediction platform ProTox- 3.0

Toxicology Mechanisms and Methods, Год журнала: 2024, Номер unknown, С. 1 - 11

Опубликована: Июль 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

Язык: Английский

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

Environmental Science & Technology, Год журнала: 2024, Номер 58(35), С. 15486 - 15496

Опубликована: Авг. 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

Язык: Английский

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Adipogenic Effects of Cresyl Diphenyl Phosphate (Triphenyl Phosphate Alternative) through Peroxisome Proliferator-Activated Receptor Gamma Pathway: A Comprehensive Study Integrating In Vitro, In Vivo, and In Silico from Molecule to Health Risk

Environmental Science & Technology, Год журнала: 2024, Номер 58(42), С. 18631 - 18641

Опубликована: Окт. 9, 2024

Cresyl diphenyl phosphate (CDP), a novel organophosphate ester (OPE), has been detected in various environmental and human samples. However, there is very limited knowledge regarding its toxicity, mechanisms of action, potential health risks. Using new alternative methods (NAMs), across the molecular interactions, signaling pathways, cell functions, animal effects, population risks, we investigated adipogenic effects associated risks CDP legacy OPE triphenyl (TPHP) by acting on peroxisome proliferator-activated receptor gamma (PPARγ). Among 19 screened OPEs, bound to PPARγ with highest binding potency, followed TPHP. activated through fitting into pocket strong hydrophobicity hydrogen bond interactions; exhibited higher potency compared In 3T3-L1 cells, enhanced PPARγ-mediated adipogenesis activity, exhibiting greater than The intracellular concentration receptor-bound concentrations (RBC) were also those TPHP both HEK293 cells cells. mice, exposure pathway, leading an increased white adipose tissue weight gain. Overall, could bind activate PPARγ, thereby promoting preadipocyte differentiation development tissue. Its obesogenic should be high concern.

Язык: Английский

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

Environmental Toxicology, Год журнала: 2023, Номер 38(7), С. 1484 - 1493

Опубликована: Март 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.

Язык: Английский

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

Journal of Applied Toxicology, Год журнала: 2024, Номер 44(7), С. 965 - 977

Опубликована: Фев. 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.

Язык: Английский

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New insights into the mechanism of triphenyl phosphate and its metabolite diphenyl phosphate in diabetic kidney disease

Ecotoxicology and Environmental Safety, Год журнала: 2025, Номер 291, С. 117877 - 117877

Опубликована: Фев. 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.

Язык: Английский

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