CHEMICAL RESEARCH IN TOXICOLOGY
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2022
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IF 3.973
Juan Wang,Guo-Dong Dai
Brominated flame retardants (BFRs) are ubiquitous industrial chemicals. In China, BFRs that are applied in large quantities include decabromodiphenyl ether (BDE-209), tetrabromobisphenol A (TBBPA), and hexabromocyclododecane (HBCD). Although findings are not always unequivocal, mounting evidence in vivo suggests that the BFRs have potential neurotoxicity. The present study aimed to assess and compare the neurotoxic effects of these three BFRs’ exposure. Male mice were orally exposed to BDE-209, TBBPA, or HBCD at 50 and 100 mg/kg bw/day for 28 days. The cognitive behavior, oxidative stress (ROS, MDA, and GSH), apoptosis-related genes (caspase-3, bax, and bcl-2), memory-related proteins (BDNF and PSD-95), and neurotransmitters (AChE and ChAT) were detected comparatively. Results showed that high doses of BDE-209, TBBPA, and HBCD exposure impaired spatial memory of mice, elevated ROS and MDA and reduced GSH levels of hippocampus, upregulated caspase-3 and bax expressions, decreased BDNF and PSD-95 levels, and disordered AChE and ChAT levels. Notably, BDE-209 caused greater adverse effects > HBCD > TBBPA. This study confirms and extends that these three BFRs had similar neurotoxic effects at current concentrations, although they may be more or less toxic.
研究领域:
毒理学
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环境健康
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
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2021
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IF 7.086
Siyan Che,Sunni Chen,Shiqi Li,Zheng Ruan
Decabromodiphenyl ether (BDE-209) tends to accumulate in lipid-rich tissues and targets the liver since its high lipophilicity. This study aimed to investigate the effects of BDE-209 on mouse liver and reveal the underlying toxicological mechanisms. Here we firstly confirmed that treatment of BDE-209 could lead to an imbalance of redox and promote apoptosis with a mitochondria-dependent manner in mice livers. Next, the transmission electron microscope (TEM) image revealed BDE-209 induced changes in mitochondrial morphology and increased endoplasmic reticulum (ER) - mitochondrial contact. ER stress was involved in the apoptosis process, which was displayed by the enhancive ER stress makers . Finally, from the increased abundance of cellular pivotal Ca 2+ signals transducer CaM, activating Ca 2+ release channel Sig-1R and IP3R1, and the stronger fluorescence density of mitochondria-specifically Ca 2+ labeled probe Rhod-2 in vitro , we summarized that there was overloaded mitochondrial Ca 2+ in hepatocytes of BDE-209 treated mice. In conclusion, these results partly illustrated evidence to reveal a potential mechanism of BDE-209-induced hepatoxicity, where oxidative stress-induced-ER stress led to the over-release of Ca 2+ , followed by the overloaded mitochondrial Ca 2+ , and cell apoptosis initiated. Our findings provided a theoretical basis for further studying.
研究领域:
毒理学
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细胞生物学
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肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2023
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IF 6.8
Yan Wang,Yue Zhang,Jinglong Xue,Leqiang Gao,Xiangyang Li,Moxuan Zhao,Dong Zhao,Xianqing Zhou
Decabromodiphenyl ether (BDE-209) is an environmental toxin. Increasing evidence showed that BDE-209 exposure induced liver injury, but the mechanism still remains unknown. The present study explored the effect and mechanism of ferroptosis on hepatotoxicity triggered by BDE-209 in vivo and in vitro . In vivo experiment, ICR mice were exposed to BDE-209 for 50 days, and then recovered for 50 days; HepG2 and L02 cells were treated with BDE-209 or/and ferrostatin-1 (Fer-1) for establishing in vitro model. In vivo , the results showed that BDE-209 accumulated in liver and induced liver damage, increased Fe 2+ and MDA contents, and blocked the activation of SLC7A11/GSH/GPX4 pathway in liver; BDE-209 also activated IKK/IκB/NF-κB pathway and elevated inflammatory cytokines levels in liver after exposure for 50 days. After BDE-209 stopping exposure 50 days, the severity of liver damage, ferroptosis and inflammatory response were still higher than the corresponding control group. In vitro , ferroptosis inhibitor Fer-1 rescued ferroptotic damage and attenuated cell death in BDE-209-treated HepG2 and L02 cells. In addition, Fer-1 reversed the activation of IKK/IκB/NF-κB pathway and the increase of pro-inflammatory cytokines levels in BDE-209-treated HepG2 and L02 cells. Together, the above results suggested that BDE-209 induced tissue damage and inflammatory response by activating ferroptosis through increasing iron-dependent lipid peroxidation and blocking the activation of SLC7A11/GSH/GPX4 pathway in liver, indicating that ferroptosis is a potential mechanism for BDE-209-induced hepatotoxicity.
研究领域:
毒理学
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肝病学
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细胞生物学
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环境科学
✓ 已验证
DOI
PubMed
高影响因子
WATER RESEARCH
·
2023
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IF 12.8
Nannan Wu,Wenrui Xiang,Feng Zhu,Zongli Huo,Zunyao Wang,Ruijuan Qu
This work was to investigate the transformation of coexisting decabromodiphenyl ether (BDE-209) on microplastics and their possible interactions in UV/chlorine process. Compared with pristine microplastics, the highly aged polystyrene (PS) showed an inhibitory effect on degradation of BDE-209. Increasing initial concentration of BDE-209 on PS inhibited degradation, while the chlorine concentration and pH did not affect the final degradation efficiency. Moreover, the presence of NO 3 − , SO 4 2− , HCO 3 − and HA in water was unfavorable for BDE-209 degradation. According to the experimental and calculation results, the contribution to the degradation of BDE-209 was ranked as direct photolysis > HO• > •Cl in the UV/ chlorine system. Chlorination products released by PS during UV/chlorination were detected. Four possible reaction pathways of BDE-209 were proposed, which mainly involved debromination, hydroxylation, chlorine substitution, cleavage of ether bond, and intramolecular elimination of HBr. It was worth noting that PS microplastics not only inhibited the degradation of BDE-209, but also affected the type and abundance of its transformation products. Meanwhile, interaction products of PS and BDE-209 were determined, which was attributed to reactions of PS-derived radicals with •Br/•C 6 Br 5 and •Cl. Results of toxicity evaluation showed that the introduction of carbon-halogen bonds, especially C-Br bond, increased the toxicity of chain scission products of PS. This work provides some new insights into transformation, interaction, and associated ecological risks of coexisting microplastics and surface adsorbed contaminants in the UV/chlorine process of drinking water treatment plants (DWTPs) and wastewater treatment plants (WWTPs).
研究领域:
环境科学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2021
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IF 6.025
Jinwen Yuan,Siyan Che,Zheng Ruan,Luqing Song,Rongxue Tang,Li Zhang
Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants (POPs). They are constantly detected in foods . PBDEs can disrupt the intestinal flora , but enterotoxicity is unknown. Luteolin , one kind of flavonoid , has drawn increasing interest as an agent that strengthens the intestinal barrier. This study aimed to evaluate the mitigating effect of luteolin on damage to the intestinal barrier induced by decabromodiphenyl ether (BDE-209) in a Caco-2 cell monolayer model. Results showed that luteolin mitigated BDE-209-induced damage to intestinal epithelial barrier by reducing the levels of reactive oxygen species (ROS), increasing the activity of superoxide dismutase (SOD) and glutathione (GSH), suppressed the secretion of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), and increased the expression of tight junction (TJ) proteins (ZO-1, occludin, and claudin-1). Furthermore, the protective effects were related to the inhibition of extracellular regulated protein kinases (ERK) and nuclear factor kappa-B (NF-κB)/myosin light chain kinase (MLCK) signaling pathways, and the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. This study is the first to provide strong evidence that BDE-209 can damage the intestinal barrier, and we here investigated the important protective effect of luteolin, which may lay the foundation for the development of luteolin as a dietary supplement to strengthen the intestinal barrier.
研究领域:
毒理学
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药理学
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细胞生物学
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环境健康
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY
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2017
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IF 2.625
Weiyi Chen,Xiaojun Niu,Jie Wang
A series of graphene oxide (GO)/Ag 3 PO 4 composites were synthesized using ion exchange-chemical precipitation method with different GO content, and the photocatalytic reduction degradation effect on decabromodiphenyl ether (BDE-209) over GO/Ag 3 PO 4 was also studied. The optimized composite exhibited superior photocatalytic activity. When the content of GO was 7%, the degradation efficiency of BDE-209 could reach 97.33% in anoxic water with methanol as electron donors after 8 h of visible light irradiation, being 3 times that over pure Ag 3 PO 4 and the BDE-209 reduction generated 3Br-8Br PBDEs congeners. The photocatalytic degradation of BDE-209 has been further investigated under different reaction conditions, such as photocatalyst dosage and pH of reaction system. According to analysis of the intermediates’s generation, accumulation and distribution, we proposed that the BDE-209 reduction mechanism was the multi-electron reduction process. GO not only trapped electrons to improve the charge separation on Ag 3 PO 4 , but also fleetingly transferred the accumulated electrons to BDE-209. This study indicates that GO/Ag 3 PO 4 could be a promising material for environmental treatment of persistent pollutants.
研究领域:
环境科学
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材料科学
✓ 已验证
DOI
高影响因子
ENVIRONMENTAL POLLUTION
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2025
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IF 7.3
Ziyan Wang,Wei Zhang,Ziyan Liu,Danyang Huang,Huiwen Kang,Jingyu Wang,Guangyu Jiang,Ai Gao
BDE-209 has a causal relationship with adverse health outcomes. However, research on its effect on bone homeostasis is relatively lacking. This study examined the relationship between BDE-209 exposure and bone health, as well as the underlying mechanisms, using both in vitro and in vivo models. In animal studies, female SD rats were administered BDE-209 for 60 days. Bone mineral density, bone microstructure, gut microbiota, and inflammaging markers were measured. Furtherly, THP-1 cell-derived macrophages were treated with a culture medium containing population-relevant dose of BDE-209 or sodium butyrate. The expression of M1 macrophage markers, osteoclast markers, and inflammatory cytokines was measured. Then macrophages were induced by osteoclast conditioned medium to evaluate the effect of BDE-209 on their differentiation into osteoclasts. Results showed reduced humeral bone density, enhanced osteoclast activity, upregulation of IL-1β, TNF-α, IL-6, and activation of PGC-1α/NAD + /cGAS-STING in the exposed group. 16s sequencing revealed that BDE-209 disrupts the abundance of the gut microbiota, notably a reduction in Lachnospiraceae . In vitro, BDE-209 can stimulate macrophages to differentiate more osteoclasts and activate the cGAS-STING pathway, while sodium butyrate can inhibit these effects. This study reveals that gut microbiota dysbiosis is involved in BDE-209-induced bone homeostasis disorder through inflammatory aging and sodium butyrate can mitigate this effect. Overall, this study provides research data for the precaution and treatment of osteoporosis associated with BDE-209 exposure.
研究领域:
毒理学
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免疫学
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骨生物学
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微生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
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2024
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IF 7.6
Ziyan Wang,Wei Zhang,Danyang Huang,Huiwen Kang,Jingyu Wang,Ziyan Liu,Guangyu Jiang,Ai Gao
Decabromodiphenyl ether (BDE-209) has been universally detected in environmental media and animals, but its damage to ovarian function and mechanism is still unclear, and melatonin has been shown to improve mammalian ovarian function. This study aimed to investigate the toxic effects of BDE-209 on the ovary and tried to improve ovarian function with melatonin. Herein, BDE-209 was administered orally to female SD rats for 60 days. Enzyme-linked immunosorbent assay, HE staining, transcriptome analysis, qPCR and immunohistochemical staining were used to explore and verify the potential mechanism. We found that BDE-209 exposure had effects on the ovary, as shown by abnormal changes in the estrous cycle, hormone levels and ovarian reserve function in rats, while increasing the proportion of collagen fibres in ovarian tissue. In terms of mechanism, cuproptosis, a form of cell death, was identified to play a crucial role in BDE-209-induced ovarian dysfunction, with the phenotype manifested as copper salt accumulation in ovary, downregulation of glutathione pathway metabolism and copper transfer molecule ( ATP7A/B ), and upregulation of FDX1 , lipoic acid pathway ( LIAS, LIPT1 ), pyruvate dehydrogenase complex components (DLAT, PDHB, PDHA1 ), and copper transfer molecule ( SLC31A1 ). Furthermore, possible interventions were explored. Notably, a supplement with melatonin has a repair effect on the damage to ovarian function by reversing the gene expression of cuproptosis-involved molecules. Overall, this study revealed that cuproptosis is involved in BDE-209-induced ovarian damage and the beneficial effect of melatonin on ovarian copper damage, providing evidence for the prevention and control of female reproductive damage induced by BDE-209.
研究领域:
毒理学
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生殖生物学
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药理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF THERMAL BIOLOGY
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2025
·
IF 2.9
Pengyun Qiao,Le Li,Zilong Li,Feifan Sun,Fa Ren
Sperm damage resulting from exposure to environmental toxicants or elevated temperatures frequently involves overlapping mechanisms, most notably the induction of mitochondrial oxidative stress. Lycium barbarum polysaccharide (LBP), a bioactive dietary component, mitigates decabromodiphenyl ether (BDE-209)-induced human sperm toxicity by modulating oxidative stress and apoptosis. Exposure to environmentally relevant levels of BDE-209 (40-80 μmol/L) significantly impaired sperm quality, as evidenced by reduced motility, compromised membrane and acrosome integrity, and increased DNA fragmentation when compared to the control group at 37 °C. Mechanistically, exposure to BDE-209 induces mitochondrial oxidative stress, resulting in reactive oxygen species (ROS) accumulation, decreased mitochondrial membrane potential (MMP), and reduced ATP production. This is evidenced by increased activities of Caspase3 and Caspase9, elevated levels of BAX, and decreased expression of BCL-2. LBP intervention (100 μg/mL) effectively scavenged ROS, restored mitochondrial potential, and enhanced antioxidant capacity, as demonstrated by increased superoxide dismutase (SOD) and glutathione (GSH) levels, alongside decreased malondialdehyde (MDA) levels. Furthermore, LBP suppressed apoptotic pathways and enhanced sperm-zona pellucida binding after BDE-209 exposure. A proposed mechanism summarizing this protective pathway is presented in the Graphical . As a naturally occurring polysaccharide that protects against oxidative stress in sperm, LBP could represent a promising candidate for dietary interventions in populations exposed to elevated levels of BDE-209. This warrants further investigation in in vivo models.
研究领域:
生殖毒理学
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环境健康
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氧化应激生物学
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男科学
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营养生物化学
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线粒体生理学
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2019
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IF 4.527
Shaojun Liang,Shengxian Liang,Hui Zhou,Nuoya Yin,Francesco Faiola
2′,2′,4,4′-tetrabromo diphenyl ether (BDE-47), one of the most abundant congeners of commercial pentaBDE utilized as flame retardants , has been phased out of production due to its potential neural toxicity and endocrine disrupting activities, and yet still present in the environment. Several alternatives to BDE-47, including tetrabromobisphenol A (TBBPA), tetrabromobisphenol S (TBBPS), tetrachlorobisphenol A (TCBPA) and decabromodiphenyl ether (BDE-209), are presently employed without restrictions and their potential toxic effects on human neural development are still unclear. In this study, we utilized a human neural stem cell (hNSC)-based system to evaluate the potential developmental neurotoxic effects of the above-mentioned five chemicals, at environment and human exposure relevant concentrations. We found that those compounds slightly altered the expression of hNSC identity markers ( SOX2 , SOX3 and NES ), without impairing cell viability or proliferation, in part by either modulating glycogen synthase kinase 3 beta (GSK3β) signaling (TBBPS, TCBPA and BDE-47), and slightly disturbing the NOTCH pathway (TBBPA, TBBPS and TCBPA). Moreover, the five chemicals seemed to alter hNSC differentiation by perturbing triiodothyronine (T3) cellular signaling. Thus, our findings suggest that the five compounds, especially TBBPS, TCBPA, and BDE-47, may affect hNSC self-renewal and differentiation abilities and potentially elicit neural developmental toxicity.
研究领域:
神经科学
·
毒理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2026
·
IF 6.1
Shaoying Gong,Jiachen Zheng,Lin Wang,Ruoyu Wu,Jianchun Han,Yongxin She
Decabromodiphenyl ether (BDE-209), a widely used polybrominated diphenyl ether, is a persistent environmental pollutant with intestinal toxicity. Arabinogalactan possesses antioxidant and anti-inflammatory properties, but its ability to counteract BDE-209-induced intestinal epithelial barrier (IEB) damage remains unclear. This study examined the protective effects of arabinogalactan on BDE-209-induced IEB damage and the underlying mechanisms. Arabinogalactan significantly restored barrier integrity, as evidenced by increased transepithelial electrical resistance and reduced FITC-dextran permeability. Mechanistically, it attenuated oxidative stress by regulating the levels of reactive oxygen species, glutathione, and malonaldehyde and the activity of superoxide dismutase and reducing the secretion of inflammatory cytokines (IL-1β, IL-6, and TNF-α). Arabinogalactan also preserved tight junction protein expression (claudin-1, zonula occludens [ZO]-1, occludin), lowered intracellular Ca²⁺, and activated the Nrf2/HO-1/NQO1 pathway. Taken together, these findings suggest that arabinogalactan inhibits oxidative stress and inflammation by regulating the Nrf2/NQO1/HO-1 signaling pathway to upregulate TJ expression, thereby alleviating BDE-209-induced IEB damage.
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2019
·
IF 4.527
Shengxian Liang,Shaojun Liang,Nuoya Yin,Francesco Faiola
The liver is one of the major targets of hormones, including thyroid hormones (THs), and many industrial chemicals, such as endocrine-disrupting chemicals. Those compounds may permeate the placenta barrier and pose a risk for embryonic development . Therefore, it is necessary to assess the toxic effects of those kind of industrial chemicals during liver development. In this study, to mimic liver specification in vitro, we differentiated human embryonic stem cells (ESCs) into functional hepatocyte-like cells. We performed this differentiation process in presence of two THs, triiodothyronine (T3) and thyroxine (T4), with the purpose of identifying biomarkers for toxicity screening. TH exposure (3, 30 and 300 nM) yielded to hepatocytes with impaired glycogen storage ability and abnormal lipid droplets’ accumulation. Global gene expression analysis by RNA-seq identified a number of genes responsible for hepatic differentiation and function which were affected by 30 nM T3 and T4. Those differentially expressed genes were used to assess the potential developmental liver toxicity of two famous environmental pollutants, 2, 2, 4, 4-tetrabromodiphenyl ether (BDE-47) and decabromodiphenyl ether (BDE-209), at 10 nM to 1 μM treatments. Our findings demonstrate that BDE-47 and BDE-209, dysregulated pathways such as “chemical carcinogenesis”, “steroid hormone biosynthesis” and “drug metabolism-cytochrome P450”. Moreover, we were able to identify a set of 17 biomarkers, very useful to predict the potential developmental hepatotoxicity of industrial chemicals.
研究领域:
毒理学
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干细胞生物学
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发育生物学
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环境科学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）